Chemical synthesis and molecular docking study of new thiazole, thiophene, and thieno[2,3-d]pyrimidine derivatives as potential antiproliferative and antimicrobial agents

This context deals with the design and synthesis of a new set of derivatives containing thiazole, thio-phene, and thieno[2,3-d]pyrimidine motifs 3-13 starting with 2-((2-methoxyphenyl)amino)acetonitrile 1 . In vitro antiproliferative activity of all the new compounds was evaluated against three cancer cell lines (HepG-2, MCF-7, and HCT-116). The safety margins of the most active antiproliferative candidates 3 and 11 were further examined against the normal human diploid cell line WI-38. Furthermore, the multi-kinase suppression effects of compounds 3 and 11 were assessed against Vascular Endothelial Growth Factor Receptor (VEGFR-2), human epidermal growth factor receptors (EGFRWT and HER-2) and compared with sorafenib and erlotinib as reference drugs. Additionally, these two compounds were investigated for their impact on the cell cycle and apoptosis induction potential in the human breast cancer cell line (MCF-7) as well as their effects on the apoptotic parameters; Bax, Bcl-2, and caspase-3. Moreover, the antimicrobial activity of all the new analogs was evaluated against various pathogenic gram-positive, gram-negative bacteria, yeast, and fungi in comparison to ampicillin and clotrimazole as reference drugs. Interestingly, both compounds 3 and 11 exhibited the most promising microbial inhibitory effect. Finally, molecular docking studies revealed promising binding patterns of compounds 3 and 11 with the prospective tar-gets, VEGFR-2, EGFRWT, and HER-2.(c) 2022 Published by Elsevier B.V.