Synthesis and antimicrobial evaluation of some 1-(4-arylthiazol-2-yl)-1′-(aryl/heteroaryl)-3,3′-dimethyl-[4,5′-bi-1H-pyrazol]-5-ols

A series of sixteen 1-(4-arylthiazol-2-yl)-1'-(aryl/heteroaryl)-3,3'-dimethyl-[4,5'-bi-1H-pyrazol]-5-ols (7a-p) was synthesized starting from dehydroacetic acid (DHA, 1) via the stepwise formation of thiosemicarbazone (2), 3-(1-(2-(4-arylthiazol-2-yl) hydrazono) ethyl)-4-hydroxy-6-methyl-2H-pyran-2-ones (4a-d) and 1-(1-(4-arylthiazol-2-yl)-5-hydroxy-3-methyl-1H-pyrazol-4-yl)butane-1,3-diones (5a-d) in high yields. The in vitro antibacterial and antifungal activities of the synthesized bipyrazoles 7a-p were investigated against two Gram-positive bacterial strains, viz. Bacillus subtilis (MTCC 441) and Staphylococcus aureus (MTCC 7443), one Gram-negative bacterial strain, viz. Escherichia coli (MTCC 42), and two fungal strains, viz. Candida albicans (MTCC 183) and Aspergillus niger (MTCC 282). The compounds 7a and 7e were found to exhibit better inhibitory activity against A. niger than the reference fluconazole. Moreover, the antifungal activities of the title compounds were more prolific than their antibacterial activities. Furthermore, in order to study binding interactions, docking simulations of compounds 7a, 7m and 7o were performed into the active site of S. aureus 1,4-dihydroxy-2-naphthoyl-CoA synthase.