Abstract
•Design and synthesis of a new set of thiazole, thiophene, and thieno[2,3-d]pyrimidine derivatives 3-13.•Compounds 3-13 were evaluated in vitro for their antiproliferative activities against HepG-2, MCF-7, and HCT-116 cell lines, and for their antimicrobial activities against various pathogenic gram-positive, gram-negative bacteria, yeast, and fungi.•Compounds 3 and 11 were assessed in vitro against VEGFR-2, EGFRWT, and HER-2.•Compound 11 was investigated for its impact on the cell cycle and apoptosis induction as well as its effect on Bax, Bcl-2, and caspase-3.•Molecular docking studies exhibited promising binding patterns of compounds 3 and 11 with VEGFR-2, EGFRWT, and HER-2.
This context deals with the design and synthesis of a new set of derivatives containing thiazole, thiophene, 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 targets, VEGFR-2, EGFRWT, and HER-2.