Day 1 :
Keynote Forum
Sahar I Mostafa
Professor in Pharmaceutical Department
Keynote: New transition metal complexes of Enantiomeric D- and L-Benzimidazol derivatives in presence of dinitrogen or phosphorous aromatic donors; synthesis, characterization and DNA interaction
Time : 10:00
Biography:
Sahar I Mostafa is a Professor of Inorganic Chemistry at Chemistry Department, Faculty of Science, Mansoura University, Egypt since 2008, Visiting Professor at Chemistry Department, McGill University, Montreal, Canada since 2009. She has developed several aspects of O,O; N,O; N,S and N,O,S low cytotoxic-organic transition metal complexes. Her current research interest is on the synthesis, characterization, reactivity and applications of O,O; N,O; N,S and N,O,S low or non-cytotoxic organic transition metal complexes in particular for biology, particularly, anticancer, for catalytic oxidation of organic substrates using transition metal complexes at higher oxidation states and catalytic epoxidation of olefins using transition metal complexes immobilized on Modified Solid Supports (MSS) such as zeolite, silica, cellulose and chitosan in heterogeneous catalytic systems. She has written several chapters in books including MSS transition metal complexes. She is the principal author of about 50 publications and co-author of 20 publications. She is a Member in the Editorial Boards and Reviewer in many Inorganic, Bioinorganic and Catalysis journals. Her academic efforts have been recognized nationally by Al-Azhar University Award (2007, 2009, 2011), Who’s is Who’s in the world (2008) and Lecturer Award from Mansoura University for Excellence in Graduate Teaching (1992).
Abstract:
In the pharmacological field, it is very important to prove the efficacy of chiral or enantiopure drugs; i.e., single enantiopure drugs have been shown to be better due to its safe and potent effect in comparison to the racemate drugs. Chiral drugs are assumed to be therapeutically active as most of the bio-targets of drugs are chiral in nature. Thus, considerable attention has been paid to chiral molecules design and construct that are versatile in occupying the active site, possess a metal-binding domain and have a bioactive organic functionality (pharmacophore), which pre-orients the molecule as a drug entity and reduces the toxicity parameters. The introduction of chirality enhances the pharmacological behavior of a metal complex by adopting a specific conformation and a target selective binding affinity for DNA (as DNA itself exists in nature only in one chiral form). The design of metal-based pharmaceuticals depends on the donor framework, the metal ion and its oxidation state. The donors can significantly alter the biological properties by modifying reactivity or substitution inertness. Tailored, multifunctional donors introduced into the metal-based medicinal agents facilitate metal ion redistribution, limit the adverse effects of metal ion overload and inhibit selected metalloenzymes. Therefore, chiral metal complexes have a promising future as robust chemotherapeutic agents in medicinal inorganic chemistry. This study is aimed to preparation of new chiral nucleases derived from ï„- and ïŒ-benzimidazol derivative (H2bie) complexes of Zn(II), Pd(II), Pt(II) and Ag(I), in absence and presence of 2,2’-bipyridyl, 1,10-phenanthroline and triphenylphosphine frameworks. Their structures are discussed on the bases of spectroscopic (IR, Raman, UV-Vis, NMR (1H, 13C and 31P) and mass), elemental analysis, molar conductivity and thermal degradation measurements. The in vitro anticancer activity of free ï„-H2bie and ïŒ-H2bie and their complexes were evaluated against two of the most famous, human breast cancer (MDA-MB231) and human ovarian cancer (OVCAR-8) cell lines. The enantio-selective complex DNA binding by circular dichroism (CD) furnishes direct information on how the DNA helix and enantiomeric complexes interact and thus reveal the influence of each enantiomer of a given complex on the DNA-binding strength. Comparisons of the CD spectra of pair of enantiomers, ï„-H2bie and ïŒ-H2bie complexes in 5 mM phosphate buffer 50 mM NaCl (pH 7.2) have been measured and the results indicate intercalative CT-DNA binding capabilities.
Keynote Forum
Oleg Reva
Associate professor in Bioinformatics
Keynote: Genetic insight into antibiotic resistance reversion in multidrug resistant tuberculosis by iodine-containing nanomolecular complex FS-1
Time : 11:00-11:30
Biography:
Oleg Reva has completed his PhD from Kiev State University, Ukraine and Postdoctoral studies from High School of Medicine, Hannover, Germany. He is an Associate Professor in the Centre for Bioinformatics and Computational Biology at the University of Pretoria. He has published more than 90 papers in reputed journals, H-index 20, NRF rating C2.
Abstract:
Drug induced reversion of antibiotic resistance is considered as a promising way to combat multidrug resistant infection that nowadays became a major threat to human health. Despite a general recognition of this opportunity, little studies were performed in the world to elucidate this phenomenon mainly because of the lack of reliable experimental models. An innovative anti-tuberculosis drug FS-1 was accepted for clinical use in Kazakhstan in 2015. Clinical trials and in vitro experiments revealed ability of this drug to induce reversion of antibiotic resistance in MDR-TB. A series of experiments on laboratory animals infected with the MDR-TB strain Mycobacterium tuberculosis SCAID 187.0 was performed for a systemic study of the drug resistance reversion phenomenon. The initial strain SCAID 187.0 was sequenced and the complete genome was deposited in NCBI (CP012506.1). Multiple Mtb isolates were collected at different stages of the experiment from the animals treated with traditional antibiotics with antibiotics supplemented with FS-1 in different concentrations and those which were left without treatment. The Mtb isolates were sequenced by Illumina and variant calling was performed. Bioinformatic analysis of the trends of genomic changes confirmed the theoretically predicted induced synergy mechanism of the drug resistance reversion. To our best knowledge, this experiment was the first systemic study of the drug resistance reversion phenomenon.
Keynote Forum
Oleg Reva
Associate Professor in the Centre for Bioinformatics and Computational Biology
Keynote: Genetic insight into antibiotic resistance reversion in multidrug resistant tuberculosis by iodine-containing nanomolecular complex FS-1
Time : 11:00
Biography:
Oleg Reva has completed his PhD from Kiev State University, Ukraine and Postdoctoral studies from High School of Medicine, Hannover, Germany. He is an Associate Professor in the Centre for Bioinformatics and Computational Biology at the University of Pretoria. He has published more than 90 papers in reputed journals, H-index 20, NRF rating C2.
Abstract:
Drug induced reversion of antibiotic resistance is considered as a promising way to combat multidrug resistant infection that nowadays became a major threat to human health. Despite a general recognition of this opportunity, little studies were performed in the world to elucidate this phenomenon mainly because of the lack of reliable experimental models. An innovative anti-tuberculosis drug FS-1 was accepted for clinical use in Kazakhstan in 2015. Clinical trials and in vitro experiments revealed ability of this drug to induce reversion of antibiotic resistance in MDR-TB. A series of experiments on laboratory animals infected with the MDR-TB strain Mycobacterium tuberculosis SCAID 187.0 was performed for a systemic study of the drug resistance reversion phenomenon. The initial strain SCAID 187.0 was sequenced and the complete genome was deposited in NCBI (CP012506.1). Multiple Mtb isolates were collected at different stages of the experiment from the animals treated with traditional antibiotics with antibiotics supplemented with FS-1 in different concentrations and those which were left without treatment. The Mtb isolates were sequenced by Illumina and variant calling was performed. Bioinformatic analysis of the trends of genomic changes confirmed the theoretically predicted induced synergy mechanism of the drug resistance reversion. To our best knowledge, this experiment was the first systemic study of the drug resistance reversion phenomenon.
Keynote Forum
Oleg Reva
Associate Professor in the Centre for Bioinformatics and Computational Biology
Keynote: Genetic insight into antibiotic resistance reversion in multidrug resistant tuberculosis by iodine-containing nanomolecular complex FS-1
Time : 10:20-11:30
Biography:
Oleg Reva has completed his PhD from Kiev State University, Ukraine and Postdoctoral studies from High School of Medicine, Hannover, Germany. He is an Associate Professor in the Centre for Bioinformatics and Computational Biology at the University of Pretoria. He has published more than 90 papers in reputed journals, H-index 20, NRF rating C2.
Abstract:
Drug induced reversion of antibiotic resistance is considered as a promising way to combat multidrug resistant infection that nowadays became a major threat to human health. Despite a general recognition of this opportunity, little studies were performed in the world to elucidate this phenomenon mainly because of the lack of reliable experimental models. An innovative anti-tuberculosis drug FS-1 was accepted for clinical use in Kazakhstan in 2015. Clinical trials and in vitro experiments revealed ability of this drug to induce reversion of antibiotic resistance in MDR-TB. A series of experiments on laboratory animals infected with the MDR-TB strain Mycobacterium tuberculosis SCAID 187.0 was performed for a systemic study of the drug resistance reversion phenomenon. The initial strain SCAID 187.0 was sequenced and the complete genome was deposited in NCBI (CP012506.1). Multiple Mtb isolates were collected at different stages of the experiment from the animals treated with traditional antibiotics with antibiotics supplemented with FS-1 in different concentrations and those which were left without treatment. The Mtb isolates were sequenced by Illumina and variant calling was performed. Bioinformatic analysis of the trends of genomic changes confirmed the theoretically predicted induced synergy mechanism of the drug resistance reversion. To our best knowledge, this experiment was the first systemic study of the drug resistance reversion phenomenon.
- Advancement in Pharmaceutical Technology
Industrial and Pharmacy Practise
Pharmaceutical Chemistry
Pharmacological vitality of drugs
Location: Central 2
Chair
Sahar. I. MostafaPr
Processor in Pharmaceutical Department
Co-Chair
Eman S. El-Leithy
Professor in Pharmaceutics
Session Introduction
Roman Hájek
University of Ostrava, Czech Republic
Title: Toward the Cure - Multiple Myeloma
Time : 11:40-12:05
Biography:
Roman Hajek is the Head of Department of Hemato Oncology at University Hospital Ostrava and Vice-Rector for Strategy and Development at University of Ostrava. He has received his PhD in Hematology and completed degrees in Internal Medicine (1996) and Medical Oncology (1998). He was a Founder Member of Czech Myeloma Group and is its Active Chairman. He is also a Member of International Myeloma Working Group. He has published over 300 scientific articles and is an Editor of European Journal of Hematology. His research interests include multiple myeloma, bone marrow transplantation and rare monoclonal gammopathies.
Abstract:
Over the last decade, overall trends in multiple myeloma (MM), particularly in younger patients, show approximately doubling. Old “dogma” myeloma is incurable is not more true. A significant part of increasing survival rates can be attributed to new treatments for MM. The use of novel agents (proteasome inhibitors, immunomodulatory agents, recently approved monoclonal antibodies) has led to more options for patients suffering from such a heterogeneous disease as MM. Not only we have more options, but our understanding of who we should give these treatments to and when, as well as improving how we administer these drugs to make it as easy as possible for patients and clinicians is growing. The role of pharmaceutical companies in drug development is unquestionable. Huge research effort and cost is behind this impressive progress in MM treatment options starting with introduction of novel agents in preclinical phase and phase-I clinical trials and concluding with registration clinical trials phase-III. However, the role of academic research groups is crucial if complex treatment strategy is required to achieve the best outcome such as increase cure rate in multiple myeloma. There are several key hot targets for clinical trials, such as monitoring of minimal residual disease (MRD), achievement of MRD negativity and treatment of MRD. Expanding cure is probably the most challenging target for well-designed trials “Style of Total Therapy”. The presentation will review incredible progress as well as paradoxes in the treatment of multiple myeloma and key challenges and/or open questions in the world.
Marian Paluch
University of Silesia, Poland
Title: Are there simple and effective methods to improve the physical stability of amorphous drugs
Time : 12:05-12:30
Biography:
Marian Paluch has obtained his PhD in 1998 in the field of the Condensed Matter Physics from University of Silesia, Poland. He was appointed as a Visiting Scientist at the Max Planck Institute for Polymer Research in Mainz, the Naval Research Laboratory in Washington DC, the University of Akron, the Hebrew University, the University of Pisa and the University of Tennessee. He is currently the Head of the Biophysics and Molecular Physics Department at University of Silesia. He has published more than 320 papers in reputed journals and has been serving as an Academic Editor in AIP Advances since 2010.
Abstract:
It is estimated that nearly 40% of marketed drug substances in crystalline form and 75% of drug candidates are poorly soluble in water and consequently have lower bioavailability. A possible solution of this problem is to convert them to the amorphous form. This is justified by the fact that the logarithm of the ratio of crystal solubility to amorphous solubility is proportional to difference between the Gibbs free energy of crystal and amorphous state, respectively. Since the Gibbs free energy of amorphous state is always higher than crystal, thus drugs prepared in amorphous form exhibit a better water solubility than their crystalline counterparts. However, there is one serious drawback of using this strategy because the amorphous drugs are, in general, physically unstable systems. It means that they may simply re-crystalize during storage losing their original advantages. Thus, main challenge in working with the amorphous drugs is the enhancement of their physical stability. In this presentation I will talk about various methods which have been developed in our laboratory to improve the physical stability of amorphous drugs.
K. Grzybowska
University of Silesia, Poland
Title: Amorphous solid dispersions of APIs with crystallization inhibitors of different molecular weights
Time : 12:30-12:55
Biography:
Katarzyna Grzybowska has received her PhD degree in Physics at the University of Silesia in 2008. In 2012, she has completed a four-year Post doctorate in the research project "From Study of Molecular Dynamics in Amorphous Medicines at Ambient and Elevated Pressure is Novel Applications in Pharmacy" in the Institute of Physics at the University of Silesia. She is a co-author of more than 60 publications in the international peer reviewed journals from ISI list and two patents.
Abstract:
A transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides and other APIs. We examine the effect of adding large molecular weight polymer polyvinylpyrrolidone (PVP K30) and the small molecular weight excipient octaacetylmaltose (acMAL) on the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL-PVP and CEL-acMAL. We found that acMAL is a better inhibitor of recrystallization of amorphous CEL than PVP K30 deep in the glassy state (T
Rajeeta Joseph
Bharati Vidyapeeth University, India
Title: Novel Ayurvedic Approach in the Treatment of Psychosis – An Experimental Study
Time : 12:55-13:20
Biography:
Rajeeta Joseph is an Associate Professor in Department of Pharmacology at Bharati Vidyapeeth Deemed University Dental College and Hospital, Pune, India . She is currently pursuing her PhD from Bharati Vidyapeeth Deemed University, India. Her area of interest is research in traditional medicine and their scientific validation. She has worked on antitubercular activity of Lawsonia inermis. She has been working in depth on actions of an Ayurvedic medicine Unmadgajakesari – a herbomineral formulation which is used in treatment of psychosis and epilepsy for past 5 years. She has 5 publications to her credit.
Abstract:
Introduction: Schizophrenia is a complex neuropsychiatric disorder with abnormalities involving multiple neurotransmitters like dopamine, serotonin, glutamate and GABA. Unmadgajakesari (UGK) is a herbomineral formulation claimed to possess antipsychotic activity. Hence the present study was carried out to assess the antipsychotic profile of UGK. Aim: To evaluate the antipsychotic activity of UGK in animal models. Materials & Method: After doing acute and sub-acute toxicity studies of UGK, it was evaluated for its effect on dopamine, serotonin, NMDA and GABA using following animal models: Inhibition of apomorphine induced climbing (dopamine), inhibition of 5-HTP induced head twitches (serotonin), Antagonism of MK-801 induced hyper locomotion (NMDA) in mice and Antagonism of PTZ induced convulsion (GABA) in rats. For studying each neurotransmitter, animals were divided into 6 groups, each group comprising of 6 animals. Group-I: Normal control, Group-II: Vehicle-control (ghrita), Group-III: Drug control (positive control). In test groups (IV-VI) UGK was administered in doses 100 mg/kg, 200 mg/kg and 400 mg/kg in mice and 70 mg/kg, 140 mg/kg and 280 mg/kg in rats. All the drugs were given orally for 8 days. Readings were taken on day 1and 8. Results: UGK was found to be non-toxic up to dose 2000 mg/kg. Significant antidopaminergic and NMDA activity was obtained on day 1 which reduced by 8th day. Anti-serotonergic activity found on day 1 and continued to be seen on day 8. GABAergic activity was not seen on day one but was present on day 8, more than anti-serotonergic action. GABAergic activity was seen only in low dose. Efficacy of UGK was not increased with dose increment. Conclusion: Present study concluded the multi-site mechanism of UGK action in animal models of psychosis acting on dopamine, serotonin, NMDA and GABA receptors and activity changed over 8 days. GABA activity evolved over 8 days to become the major mechanism of action on long term use. None of the drugs presently available for the treatment of psychosis have such a changing profile and action on GABA.
Boitumelo Semete
Council for Scientific and Industrial Research, Pretoria, South Africa
Title: CSIR’s cutting edge tools and platform technologies that accelerate drug discovery R&D.
Time : 14:00-14:25
Biography:
Boitumelo Semete-Makokotlela is the Executive Director at CSIR Biosciences. She has a PhD in Biochemistry and also holds an MSc in Management Finance and Investment Wits Business School. She was with McKinsey & Company for 2 years. Prior to that, she was at the CSIR’s Polymers and Composites Division as a Senior Researcher. Her research team focused on developing Nanotechnology drug delivery systems for TB, HIV and Malaria. She has completed her Postdoctoral research training on Nano drug delivery systems at the University of Nottingham and EPFL, Switzerland. She has published as a first author and co-author in original papers, review articles and book chapters.
Abstract:
The long time-lines and high cost of drug discovery and development ensues. With this context, pharmaceutical companies are exploring more active partnership models with academia and Biotech companies. The high genetic variability of the African population, resulting in some of these drugs not being effective in African population and resulting in adverse toxic effects not experienced in other population groups remains critical in the African context. The CSIR has developed a number of cutting edge tools that address the factors. The first is a high throughput array printing technology that enables screening of 3000 compounds per week versus 300 per week using some of the current technologies. Through this proprietary technology, the pharmaceutical companies can time and cost efficiently, be able to screen their compounds for specific bioactivity. Secondly through our synthetic biology platform, CSIR can utilize genetic engineering tools for dry repurposing as well as screening against specific genetic backgrounds using stem cells technologies. Thirdly, CSIR’s capability in high throughput screening enables it to screen specific drugs at a high throughput against markers known to result in varied drug metabolism, resulting in toxicity. Lastly, the nanotechnology encapsulation and re-formulation platform, addresses specific limitations of bio and pharmaceutically active molecules. These technologies can improve the solubility, delay and control the release of actives as well as facilitate intracellular drug delivery and target to the site of interest. CSIR, in partnership with academic institutions is well positioned to develop tools that will result in realization of precision medicine objectives, cost and time effective screening tools, drug repurposing efforts and implement reformulated products.
Monika I. Konaklieva
American University, USA
Title: Non-transpeptidase binding lactams active against Mycobacterium tuberculosis
Time : 14:25-14:50
Biography:
Monika I Konaklieva has obtained her Doctoral degree in Organic Synthetic Chemistry from State University of New York at Buffalo (1997). She is currently an Associate Professor in the Department of Chemistry, American University, Washington, DC. In 2007, she spent her sabbatical leave at the Tuberculosis Research Section, LCID, NIAID, NIH. Her research focuses on the synthesis and evaluation of new antibacterial, neuroprotective and anticancer agents, as well as development of efficient and environmetally friendly synthetic approaches for their preparation.
Abstract:
We have designed Non-transpeptidase binding lactams active against Mycobacterium tuberculosis, synthesized and tested a novel class of non-transpeptidase, β-lactamase resistant monocyclic β-lactams that carry an arylthio group at C4; these thio ethers exhibit inhibitory and cidal highly active against the serine beta-lactamase producing Mycobacterium tuberculosis H37Rv (Mtb). Some of the compounds have demonstrated minimal inhibitory concentration (MIC) as low as 6.25 µg/ml in 7H9 and 0.19 µg/ml in GAST. Preliminary investigations indicate that these compounds are cidal to both replicating and non-replicating persistent Mtb. These compounds are promising candidates for lead optimization and target identification studies which are currently underway.
Michael du Plooy
Forrester Pharma South Africa
Title: An appraisal of accelerated evaluation process in the south african context
Time : 14:50-15:15
Biography:
Michael du Plooy is a registered Pharmacist, Pharmacologist and an admitted Attorney. He is currently employed at Forrester Pharma as a Business Executive tasked with business development, regulatory affairs and group legal responsibilities. His research was awarded the Best Publication in Basic Pharmacology for 2012 in South Africa. He has held various positions in research, pharmaceutical and legal organizations.
Abstract:
Would purpose-specific accelerated evaluation processes, e.g., breakthrough designation, promote registration of essential medicines in South Africa or lead to “forced entry” onto the Fast Track? Regulatory Authorities, the world over employ divergent processes to identify eligible medicines and earmark it for accelerated evaluation. The recent success of the United States Food and Drug Administration’s breakthrough designation initiative inspired a similar scheme by the European Medicines Agency and suggests the significance of purpose-specific accelerated evaluation processes. This discussion will explore the South African landscape in respect of accelerated evaluation processes, infer the value of purpose-specific accelerated evaluation processes, and propose how a utilitarian application thereof could broaden access to treatment.
Bakari Amuri
University of Lubumbashi, Congo
Title: Discovery of active compounds from plants used as antidiabetics in traditional medicine in DR Congo
Time : 15:15-15:40
Biography:
Bakari Amuri has obtained his Diploma in Pharmacy at the University of Lubumbashi (2008). Presently his is a Lecturer at the University of Lubumbashi. Recently, he co-published in Science an interesting paper on African Traditional Medicine.
Abstract:
Beside infectious diseases such as HIV/AIDS and malaria, type 2 diabetes mellitus is becoming a major public health problem in Africa. Access to conventional medicine being limited, Traditional Medicine (TM) remains, for most of the patients, the major and, often, the only source of care. Thus, the aim of this study was to research plants used in TM to obtain active products that can be proposed to treat diabetes. A survey of herbs used as antidiabetic in TM was conducted in Lubumbashi on 49 tradipraticians. Among 95 cited plants, 9 were selected for biological and chemical studies, based on their citation frequency and bibliographic information indicating the absence of data on antidiabetic activity. An in vivo oral glucose tolerance test was performed on Cavia porcellus L. to evaluate their antihyperglycemic activity. Bio-guided fractionation of the most active extract, Vitex madiensis Oliv (Verbenaceae) from the nine plants investigated was undertaken. Its leaves extract led to the isolation and characterization of 20-hydroxyecdysone. Biological tests indicate that this compound has a marked antihyperglycemic activity. In conclusion, tradipraticians cited both herbs already known for their antidiabetic effect (34 plants) and so far not cited herbs that proved active in our model. Thus, some plants used in TM contain active molecules and can serve as a starting point for the drug discovery. The use of biotechnology for the selection and engineering of high-level producing plants and for large scale production of interesting active molecules appears as a captivating option for a good management of natural resources.
Forcados Gilead
Ahmadu Bello University, Nigeria
Title: Phytochemicals in Khaya senegalensis ameliorates gastrointestinal oxidative stress associated with coccidiosis in broiler chickens
Time : 15:40-16:05
Biography:
Forcados Gilead Ebiegberi is currently a PhD student at the Ahmadu Bello University, Zaria, Nigeria and an elective PhD student of University of Pretoria. He works with the National Veterinary Research Institute Vom in Nigeria and has published papers in reputed journals. His research interest examines the role of phytochemicals in the amelioration of human and veterinary diseases.
Abstract:
There is growing scientific evidence for the role of phytochemicals in the prevention and control of diseases. Coccidiosis is a parasitic disease in poultry characterized by intestinal lesions, inflammation and oxidative stress, responsible for considerable economic loss due to resulting morbidity and mortality. There are unsatisfactory results from the use of live attenuated vaccines, while ionophore antibiotics are limited against antibiotic-resistant Eimeria strains in addition to growing public health concerns about the use of antibiotics in chickens due to drug residues in meat. These limitations necessitate studies on the potential of phytocompounds as anti-coccidial agents. In this study, the aqueous stem bark extract of Khaya senegalensis (200, 400, 800 mg/Kg) was evaluated for its efficacy against experimentally infected chickens using oocyst count, oxidative stress markers and hematological parameters. The positive control group consisted of infected birds treated with Amprolium (250 WSP, Kepro® B.V., Holland), while negative control was untreated. Phytochemical analysis of Khaya senegalensis showed the presence of tannin and saponin. There was a significant reduction in oocyst count and an increase in weight gain, enhanced antioxidant activity with increased glutathione, catalase, superoxide dismutase activity and decreased malondialdehyde (P<0.05) in gastrointestinal homogenates across the K. Senegalensis treated groups. There was marked increase in PCV, RBC, WBC and Hemoglobin concentration. The results show that the aqueous extract of K. senegalensis ameliorated clinical signs of coccidian infection via its antioxidant properties and may be promising for the development of phytochemical based anticoccidial therapy.
Nanfack Donfack Arno Rusel
University of Dschang, Cameroon
Title: Cytotoxicity and anti-inflammatory activity of the constituents from the roots of Pentas
Time : 16:05-16:30
Biography:
Nanfack Donfack Arno Rusel has completed his PhD degree under the supervision of Professor Pierre Tane in Organic Chemistry at the University of Dschang, Cameroon (2014) where he is currently working as a Research and Teaching Assistant at the Department of Chemistry. He has published about 5 papers in reputed journals and has been serving as Reviewer in BMC Complementary and Alternative Medicine.
Abstract:
A coumarin, cleomiscosin A and nine anthraquinones derivatives were isolated from the roots of Pentas schimperi. Their structures were elucidated by spectroscopic techniques (1H NMR, 13C NMR, HSQC, HMBC, 1H-1H COSY), mass spectrometry (EIMS, HREIMS) and by comparison with published data. The compounds were identified as 3-hydroxy-1-methoxy-2-methylanthraquinone (1), 2-hydroxymethylanthraquinone (2), schimperiquinone B (3), cleomiscosin A (4), damnacanthal (5), 1,2-dihydroxy anthraquinone (6), damnacanthol (7), 3-hydroxy-2-hydroxymethyl anthraquinone (8) for the isolated compounds and as 1-hydroxy-2-methoxyanthraquinone (9) and 2-hydroxymethyl-3-O-prenylanthraquinone (10) for the semi-synthetic derivatives. The derivative was characterized here for the first time. The cytotoxicity of compounds 3, 5, 7 and 8 against nine drug-sensitive and multidrug resistant (MDR) cancer cell lines was assessed. Compounds 5 and 7 displayed cytotoxic effects with IC50 values below 81 µM on all the nine tested cancer cell lines whilst 3 and 8 compounds displayed selective activities. The recorded IC50 values for compounds 5 and 7 ranged from 3.12 µM and 12.18 µM (towards leukemia CCRF-CEM cells) and from 30.32 µM and 80.11 µM (towards gliobastoma U87MG.ΔEGFR cells) respectively and from 0.20 µM (against CCRF-CEM cells) to 195.12 µM (against CEM/ADR5000 cells) for doxorubicin. Compounds 5 and 7 induced apoptosis in CCRF-CEM leukemia cells, mediated by the disruption of the MMP and increase in ROS production. The anti-inflammatory activity of a coumarin (4) and nine anthraquinones derivatives were determined. The anti-15-lipoxygenase activity and on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated macrophages RAW 264.7 cells were determined. The Griess assay was used to measure nitric oxide production and the ferrous oxidation-xylenol orange assay was used to determine the 15-lipoxygenase inhibitory activity. All the compounds significantly decreased nitrite+nitrate accumulation in LPS-stimulated RAW 264.7 cells in concentration dependent manner with 85.67% to 119.75% inhibition of NOx production at 20 µg per mL. Most of the compounds had moderate inhibitory effect on 15-LOX activity. Compounds 8 and 10 were the more potent inhibitor both in NOx production with respective IC50 values of 1.56 µM and 6.80 µM. Compounds 2, 7 and 8 had good anti-15-lipoxygenase activity with respective IC50 values of 13.80 µM, 14.80 µM and 15.80 µM compared to quercetin, which was used as a standard LOX inhibitor (IC50 of 16.80 µM). Anthraquinones from Pentas schimperi and mostly damnacanthal, damnacanthol are potential cytotoxic natural products that deserve more investigations to develop novel antineoplastic drugs against multifactorial drug resistant cancers. Our study revealed also damnacanthol and 3-hydroxy-2-hydroxymethyl anthraquinone as potent inhibitor of both anti-15-lipoxygenase activity and nitric oxide (NO) production.
- Medicinal inception of drugs involving Phytochemical Pharmacy
Pharmaceutical microbiology and biotechnology
Pharmaceutical equipments and instrumentation
Chair
Oleg Reva
Associate professor in Bioinformatics
Co-Chair
Keddon Powell
Associate Professor
Session Introduction
Oleg Reva
University of Pretoria, South Africa
Title: Hidden activities of known antibiotics revealed by molecular docking of batumin, mupirocin and bacillaen.
Time : 10:30-10:55
Biography:
Oleg Reva has completed his PhD from Kiev State University, Ukraine and Postdoctoral studies from High School of Medicine, Hannover, Germany. He is an Associate Professor in the Centre for Bioinformatics and Computational Biology at the University of Pretoria. He has published more than 90 papers in reputed journals, H-index 20, NRF rating C2.
Abstract:
Drug induced reversion of antibiotic resistance is considered as a promising way to combat multidrug resistant infection that nowadays became a major threat to human health. Despite a general recognition of this opportunity, little studies were performed in the world to elucidate this phenomenon mainly because of the lack of reliable experimental models. An innovative anti-tuberculosis drug FS-1 was accepted for clinical use in Kazakhstan in 2015. Clinical trials and in vitro experiments revealed ability of this drug to induce reversion of antibiotic resistance in MDR-TB. A series of experiments on laboratory animals infected with the MDR-TB strain Mycobacterium tuberculosis SCAID 187.0 was performed for a systemic study of the drug resistance reversion phenomenon. The initial strain SCAID 187.0 was sequenced and the complete genome was deposited in NCBI (CP012506.1). Multiple Mtb isolates were collected at different stages of the experiment from the animals treated with traditional antibiotics with antibiotics supplemented with FS-1 in different concentrations and those which were left without treatment. The Mtb isolates were sequenced by Illumina and variant calling was performed. Bioinformatic analysis of the trends of genomic changes confirmed the theoretically predicted induced synergy mechanism of the drug resistance reversion. To our best knowledge, this experiment was the first systemic study of the drug resistance reversion phenomenon.
Namrita Lall
University of Pretoria, South Africa
Title: South African plants and skin cancer
Time : 11:05-11:30
Biography:
Namrita Lall has completed her PhD from the University of Pretoria and was a Visiting Scientist at the University of Illinois, Chicago and Kings College London. She has published more than 100 papers in peer reviewed journals. She is also the Co-Inventor of 14 national and international patents. In 2014, she received the Order of Mapungubwe: South Africa’s highest honour from Honourable South African President, Jacob Zuma, in recognition of her research. The highlight of her academic career has been her nomination for a National Research Chair in Plant Health products from IKS, which was awarded by the NRF/DST in 2016, which is her current position at the University of Pretoria, South Africa.
Abstract:
South Africa has a wealthy supply of plants (about 23 500 species of higher plants) together with a high degree of endemicity (36.6%) in the indigenous South African flora, of which 4000 plant taxa are ethnomedicinally used and approximately 500 species are used in traditional medicine by an estimated 70% South Africans on a regular basis. South Africa has huge potential in identifying novel compounds to treat many diseases. South African plants for various purposes such as infectious diseases, cancer, skin-hyperpigmentation problems, melasma, periodontal diseases, and for ACNE problem have been scientifically investigated. Steady progress in evaluating potential medicinal plants for product development with potential in human medicine has been made. Hypopigmentation is a common problem in the Western world and there are many people – especially Caucasian skin types – with skin problems such as vitiligo, leukoderma and progressive macular hypomelanosis. There are a few treatments available for hypopigmentation disorders, but most of those are only temporary – when treatment is ceased the spots re-appear – some of them can even be harmful in the long run, such as the case with UV combined treatments. Progressive macular hypomelanosis is also a hypopigmentation disease. Progressive macular hypomelanosis differs from the other hypopigmented diseases, as it is caused by bacteria. Previous studies conducted by Relyveld et.al. showed that the causative bacteria belongs to the Propionibacterium acnes species, the same bacteria which causes acne, but it is a different strain, still unidentified. Although it is the same species which causes both acne and progressive macular hypomelanosis it is not necessary that if one has acne, the same person can have the hypo-pigmented spots or vice versa. The aim of the present study was to find an alternative treatment for progressive macular hypomelanosis, through investigating plants that could inhibit bacterial growth of P. acnes and induce melanin production in melanocytes (in vitro). The antibacterial studies also determined whether the plants were bactericidal or bacteriostatic. Combinations of different plants or the synergy between plants and known drugs were tested to find the most potent solution. Ten plants were chosen for this study, a few indigenous to South Africa. The results indicated that only one of the ten plants did not show antibacterial activity against P. acnes reference strains ATCC 6919 and ATCC 11827. The Ficus species showed 50 % inhibition of the bacteria’s growth at a concentration of 500 μg per mL, while the Pelargonium sp. Showed 50% inhibition of the bacteria’s growth at a concentration of 250 μg per mL. The Hypericum sp. and Withania sp. showed to be the most active, resulting in 50 % inhibition of the bacteria’s growth at concentrations lower than 70 μg/mL. The aforementioned concentrations needed for bacterial inhibition decreased when combined with known drugs. The cytotoxity of all the plants were also determined to ensure that the active concentrations against the bacteria are lower than the toxic concentrations of the plant extracts.
N. Mkhumbeni
Vaal University of Technology, South Africa
Title: The effect of Eucomis autumnalis osteogenic markers in vitro
Time : 11:30-11:55
Biography:
Nolutho Mkhumbeni is an Immunology and Hematology Lecturer at Vaal University of Technology (VUT). She holds a Master’s degree in Biotechnology and has received the Vice Chancellor’s Award at VUT for obtaining the highest score in the faculty. She is currently a Doctoral candidate at the Tshwane University of Technology (TUT) in Biomedical Technology. Her research interests lie in South African indigenous knowledge systems, specifically medicinal plants and their scientific validation and potential application in tissue engineering and bone regeneration. She is a recipient of the National Research Foundation (NRF) Thuthuka Research Grant for her doctoral research.
Abstract:
Medicinal plants have been used to treat diseases since time immemorial. South Africa is rich in natural medicinal resources and it has been estimated that over 60% of South Africans make use of medicinal plants that they obtain from traditional healers. The genus Eucomis is endemic to southern Africa and is part of the Hyacinthaceae family. Of the ten species within the genus, Eucomis autumnalis (Mill) Chitt Subspecies autumnalis is the most commonly used herbal remedy for postoperative recovery and the treatment of bone fractures. Its vernacular name is Umathunga, literally meaning ‘to sew (bone) together’. Fracture non-union occurs when a fracture has not healed within the expected period and is not expected to heal without intervention. Expensive treatment is required and is usually associated with multiple surgical procedures, prolonged hospital stay, pain and functional disability. This greatly increases the burden on the health care systems of developing countries. Bone morphogenetic proteins have been used to treat non-union, but they are associated with high cost and the risk of ectopic bone formation in some patients. Medicinal plants may provide a safe and cost effective alternative treatment for fracture non-union, decreasing the time it takes for the patient to return to full activity. No studies have been found investigating the potential osteoinductive activity of Eucomis autumnalis in C2C12 cells, a mouse myoblast cell line. The main aim of this study is to scientifically investigate the effect that E. autumnalis has on osteogenic markers.
Keddon Powell
University of Strathclyde, UK
Title: Application of novel continuous crystallization approaches in pharmaceutical drug manufacture
Time : 11:55-12:20
Biography:
Keddon Powell has received BSc in General Chemistry and Applied Chemistry (2007) from The University of the West Indies, Jamaica. In 2010, he has obtained his MSc in Applied Chemistry from the University of Limerick, Ireland. He has over 8 years combined industry and academic experience in Chemistry and Engineering. He has recently completed PhD in Chemical Engineering from Loughborough University, United Kingdom and has since been appointed as a Research Associate at the Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallization, University of Strathclyde.
Abstract:
Continuous manufacturing and crystallization has been an ad hoc research field in the past decade, which campaigns for the development and adoption of current generation technologies in the pharmaceutical industry. The Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallization (CMAC) aims to accelerate the adoption of continuous manufacturing processes for the production of active pharmaceutical ingredients to higher quality, at lower cost and more sustainably. A series of novel continuous manufacturing and crystallization technologies incorporating process monitoring technologies and information systems are currently been investigated to provide engineering designs that are amenable to adoption in commercial plants and robust on scale-up to industrial production capacities. It is hoped that these technologies will enable the change from batch to continuous manufacturing in the pharmaceutical sector and accelerate the adoption of quality by design (QbD) principles, that is, quality assured by better product and process understanding.
Gert Kruger,
Catalysis and Peptide Research, South Africa
Title: Preclinical HIV and TB work at the CPRU
Time : 12:20-12:45
Biography:
Hendrik Gerhardus Kruger has graduated from Potchefstroom University, South Africa, in 1996 under the supervision of Frans Martins and Attie Viljoen. He actively pursues the synthesis, computational chemistry and biotesting of cage compounds in the Catalysis and Peptide Research Unit at University of KwaZulu-Natal, South Africa.
Abstract:
The preclinical research efforts of the catalysis and peptide research unit on HIV and TB drugs will be presented. HIV-1 subtypes are unevenly distributed across sub-Saharan Africa and prevalence rates differ significantly from country to country. HIV-1 subtype C is the predominant subtype in the global epidemic and in southern Africa, the worst affected region. I will discuss hypotheses for geographic differences, present data on molecular epidemiology and discuss data from our lab that suggests unexpected subtype-specific biological differences. I will discuss possible implications of these data for disease progression and epidemic spread. The unit explores four legs of drug discovery, namely theoretical methods (molecular modeling) in drug design, drug synthesis, biophysical analytical methods and biochemical methods (including animal studies). An update on the progress of each of these aspects will be presented.
Sahar I. Mostafa
Mansoura University, Egypt
Title: New complexes containing 2-mercaptobenzothiazole and different dinitrogen or phosphorous aromatic donors; synthesis, characterization and DNA interaction
Time : 13:25-13:50
Biography:
Sahar I Mostafa is a Professor of Inorganic Chemistry at Chemistry Department, Faculty of Science, Mansoura University, Egypt since 2008, Visiting Professor at Chemistry Department, McGill University, Montreal, Canada since 2009. She has developed several aspects of O,O; N,O; N,S and N,O,S low cytotoxic-organic transition metal complexes. Her current research interest is on the synthesis, characterization, reactivity and applications of O,O; N,O; N,S and N,O,S low or non-cytotoxic organic transition metal complexes in particular for biology, particularly, anticancer, for catalytic oxidation of organic substrates using transition metal complexes at higher oxidation states and catalytic epoxidation of olefins using transition metal complexes immobilized on Modified Solid Supports (MSS) such as zeolite, silica, cellulose and chitosan in heterogeneous catalytic systems. She has written several chapters in books including MSS transition metal complexes. She is the principal author of about 50 publications and co-author of 20 publications. She is a Member in the Editorial Boards and Reviewer in many Inorganic, Bioinorganic and Catalysis journals. Her academic efforts have been recognized nationally by Al-Azhar University Award (2007, 2009, 2011), Who’s is Who’s in the world (2008) and Lecturer Award from Mansoura University for Excellence in Graduate Teaching (1992).
Abstract:
The synthesis of new complexes of 2-mercaptobenzothiazole (Hmbt), [Zn(L)(mbt)(H2O)2]Cl, [M(mbt)(L)]Cl (M(II)=Pd, Pt; L=bpy, phen), [M(mbt)(PPh3)Cl] (M(II)=Pd, Pt), [Zn(PPh3)2(Hmbt)2Cl2], [Ru(mbt)2(H2O)2], [Ru(PPh3)2(mbt)2], [Ir(mbt)3]Cl, [OsO2(mbt)2], [Rh(mbt)3(H2O)3], [Ag(Hmbt)(mbt)] and [Au(mbt)2Cl], are reported. Their structures are discussed on the bases of spectroscopic [(IR, Raman, UV-vis, NMR (1H, 13C and 31P) and mass]), elemental analysis, molar conductivity and thermal degradation measurements. The in vitro anticancer activity of Hmbt and its complexes, [Zn(L)(mbt)(H2O)2]Cl, [M(L)(Hmbt)]Cl (M(II)=Pd, Pt; L=bpy, phen) and [Ag(Hmbt)(mbt)], were evaluated against human breast cancer (MDA-MB231) and human ovarian cancer (OVCAR-8) cell lines. The CT-DNA-binding properties of [Zn(mbt)(phen)(H2O)2]Cl, [Pd(Hmbt)(phen)]Cl, [Pt(L)(Hmbt)]Cl (L=bpy, phen) and [Au(mbt)2Cl], were studied using circular dichroism (CD) spectroscopy. The CD spectral data are further supported by UV-visible titrations of [Pt(phen)(mbt)]Cl, [Pd(phen)(mbt)]Cl and [Zn(mbt)(phen)(H2O)2]Cl with CT-DNA. The results indicate that the complexes may have intercalative CT-DNA binding capabilities.
Gourav Bharat Deshmane
Bharati Vidyapeeth University, India
Title: Study efficacy of Krishnavajrabhraka Bhasma in chronic asthma
Time : 13:50-14:15
Biography:
Gourav Bharat Deshmane is currently pursuing his PhD from Bharati Vidyapeeth Deemed University Medical College. He has keen interest in Ayurvedic medicine and has worked in depth on Krishnavajrabhraka Bhasma (KVB). He has been working on this molecule for last four years and is presently trying to find out whether the reversal of bronchiolar remodeling by KVB is by stimulation of stem cells in respiratory system. He has two publications to his credit and he is also interested in statistics.
Abstract:
Introduction: Chronic asthma is chronic airway inflammation leading to hyper-responsiveness of tracheo-bronchial tree. Steroids, being anti-inflammatory, are the mainstay of the treatment but have multiple adverse reactions. Krishnavajrabhraka Bhasma (KVB) is the herbo-mineral formulation claimed to be effective in chronic asthma. Present study was carried out to assess anti-asthmatic activity of KVB. Aim: To evaluate the efficacy of Krishnavajrabhraka Bhasma (KVB) in animal models of chronic bronchial asthma. Methods: After acute, sub-acute and chronic toxicity studies, KVB was evaluated for efficacy in animal models of chronic asthma. In all the experiments, 30 animals were divided into 5 groups and accordingly treatment was given: Vehicle (water), vehicle (honey water), Low dose KVB, High dose KVB and Prednisolone. Expt.I (Bronchial hyper-reactivity): On day 1, G. pigs were sensitized with egg albumin (EA). From 22nd day, they were treated for 21 days. At the end, pre-convulsive time was noted after EA challenge. Expt.II (Bronchial remodeling): After repeated challenges with EA aerosol for 4 weeks, rats were treated for 15 days. After rechallenge, broncho-alveolar lavage fluid was collected for analysis. Animals were sacrificed & lungs removed for histopathology. Results: Expt.I: KVB in high dose showed significant (p<0.01) increase in pre-convulsive time when compared to control groups. Expt.II: KVB significantly reduced (p<0.01) total eosinophil count in lavage fluid & also bronchial smooth muscle thickness compared to control. Results in both these experiments were comparable to Prednisolone. Conclusion: KVB was found to be effective in chronic asthma.