Faculty Advisor: Kristopher v. Waynant
The synthesis, characterization, and preliminary investigation of biological activity of azothioformamides and their copper(I) and silver(I) complexes.
The redox-active azothioformamide (ATF) ligand is known to oxidatively dissolve and/or chelate to a variety of late-transition metals. Metal chelation is a key pathway in cell proliferation and a variety of compounds similar to ATF have shown increased biological activity including antimicrobial, antineoplastic, and antifungal properties promoting this mechanism as a potential inhibition route. For this study, a series of ATF compounds were synthesized utilizing various synthetic strategies and then fully characterized. Each ligand varied the electron-withdrawing or donating groups which indicate metal chelation strength. Additionally, coordination complexes of copper(I) and silver(I) salts were synthesized and fully characterized (FTIR, 1H and 13C NMR, elemental analysis, and m.p.). All substances were tested for their antimammalian activity against human lung adenocarcinoma line (A549) and human myelogenous leukemia line (K562), in addition to their antimicrobial activity against Gram (+) bacteria like (Staphylococcus aureus and Bacillus subtilis), as well as against Gram (-) bacteria like (Chromobacter violaceum, Escherichia coli, Pseudomonas aeruginosa) and yeast (Candida albicans). All ligands showed activity against A549 cells yet no activity against K562 nor various microbes indicating a potential antineoplastic specificity. Metal complexes of these ligands, specifically of silver(I), provided significantly more antibacterial and cytotoxicity activity than the parent ligand and more activity against Gram (+) cell lines. Current efforts are designed towards more targeted approaches and devising specific mechanisms of action.