The present study involved the design and synthesis of a novel series of thiazole derivatives 3, 5, 7, 8, 10–13 having various heterocyclic scaffolds, including pyrazole, pyridine, and/or pyrimidine. Upon screening of their antiproliferative efficacy, pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b, afforded excellent activity against cancerous HepG-2 and MCF-7 cell lines with safety borders against normal human diploid cell line WI-38 comparing with doxorubicin and erlotinib. Then, their impact upon the apoptotic indicators; caspase-3, Bax and Bcl-2 was assessed. Regarding to antimicrobial activities, all screened Gram-positive and Gram-negative bacteria and fungal strains except Candida albicans, were effectively inhibited by the thiazole moiety bearing pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b. Additionally, thiazole-pyrazolo[3,4-b]pyridine 5b exhibited remarkable and superior inhibitory properties against EGFR and E. coli DNA gyrase (IC50 = 0.35 ± 0.25 and 2.55 ± 0.03 µM, respectively) in comparison with references erlotinib and novobiocin (IC50 = 0.27 ± 0.02 and 3.78 ± 0.02 µM, respectively). In order to provide improved optimization and rationalization of effective novel anticancer and antimicrobial leads, in silico ADMET and docking investigations were ultimately constructed.
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