Sahar I Mostafa
Professor in Pharmaceutical Department
Title: New transition metal complexes of Enantiomeric D- and L-Benzimidazol derivatives in presence of dinitrogen or phosphorous aromatic donors; synthesis, characterization and DNA interaction
Biography
Biography: Sahar I Mostafa
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.