Synthesis and Biological Evaluation of Nitrogen and Sulfur Heterocycles

Abstract

Novel series of pyrazoline carbothioamides, acetyl pyrazoles, pyridine-3-carbonitriles, pyridine-2-carbonitriles, and nicotinonitriles were synthesized. The structures of the newly synthesized compounds were established based on their spectral data, elemental analyses and alternative synthetic routes whenever possible. Also, the newly synthesized compounds were screened for their in vitro anticancer activity against T-47D (breast cancer human cell line) and UACC-257 (melanoma human cell line) by MTT assay (a colorimetric assay for assessing cell metabolic activity). Experimental results demonstrated that all the synthesized compounds exhibited moderate to high activity against T-47D breast cancer cell line, especially compounds C5, D1, H6 and I6 surpassed that of cisplatin surpassed that of cisplatin. Compounds F3, F4 and F5 showed potent activity against UACC-257 melanoma cancer cell line and surpassed the potency of cisplatin, while the most potent compound against UACC-257 melanoma human cancer cell line was C4. Molecular docking studies were performed on compounds C5, D1, H6 and I6 in 6I5K active site. Also, molecular docking studies were carried out for compounds C4, E5, F3 and F4 in 1M17 active site using Molecular Operation Environment (MOE 2008.10) software. Also, drug-likeness, pharmacokinetics, and toxicity assessment studies were carried out.