Abstract
In our attempt to develop potential new drug candidates with promising dual antimicrobial and anticancer activities, a series of pyrazolothiazole and thiazolopyridine analogues has been synthesized. All compounds were evaluated for their antimicrobial potential towards pathogenic strains and cytotoxicity properties against hepatic cancer cell line HepG-2 and breast cancer cell line MCF-7. 9 c showed excellent antimicrobial activity against the tested strains, with MIC values about 27.5 mu M (S. epidermidis), 6.8 (B. subtilis) and 3.4 mu M (S. pneumoniae and K. pneumoniae) fold higher than the reference drug, whilst 9 a, 9 b and 5 a exhibited also potent activity against selected strains. Moreover, compounds 9 c (IC50=10.89 mu M and 15.60 mu M) and 9 a (IC50=22.24 mu M and 28.47 mu M) showed promising anticancer activity for HepG2 and MCF-7 cell lines, respectively, when compared to the known anticancer drugs, 5-Fluorouracil (IC50=26.75 mu M and IC50=32.75 mu M). The data from structure-activity relationships analysis revealed the potency of pyrazolothiazole than thiazolopyridine derivatives in generating potential activity. Further, molecular docking studies performed on the more active antimicrobial and cytotoxic compound, 9 c to get insights for binding modes to the target enzymes (PDB ID: 1JIJ) for antimicrobial, and (PDB ID: 1DI8) and (PDB ID: 3TWJ) for anticancer revealed that they interacted with the same key amino acids with TyrRS for S. aureus, CDK2 and ROCK1, respectively.