Synthesis, antimicrobial and ergosterol biosynthesis inhibition activity of clubbed 1,1′-biphenyl-pyrazole derivatives

Abstract

Microbial infections remain a grave threat to global health security due to the increase in antibiotic resistance. The ongoing coronavirus pandemic has increased the risk of microbial and fungal infections. New therapeutic agents are needed to combat microbial infections. Two series of new clubbed 1,1′-biphenyl-pyrazole have been synthesized. The newly synthesized pyrazole derivatives were evaluated for in vitro antibacterial activity against E. coli (NCIM 2574), P. mirabilis (NCIM 2388), B. subtilis (NCIM 2063), S. albus (NCIM 2178), and in vitro antifungal activity against A. niger (ATCC 504) and C. albicans (NCIM 3100). Compound 10b has shown good activity against P. mirabilis with MIC of 15.62 μg mL⁻¹. Against C. albicans, eleven pyrazole derivatives 5c, 5e, 5f, 5g, 6a, 6b, 6c, 6e, 10b, 10c, and 11a have shown good antifungal activity with MIC of 62.5–31.25 μg mL⁻¹. Also, against A. niger, seven compounds 5f, 5g, 6e, 10a, 10b, 10c, and 11b, have exhibited good activity with MIC of 62.5–31.25 μg mL⁻¹. Compounds 6e, 10c, and 11b were further evaluated and showed ergosterol biosynthesis inhibition activity. Thus, the significant antimicrobial activity of 1-(3-substituted-4′-alkoxy-3′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)-5-substituted-3-(trifluoromethyl)-1H-pyrazole, and 1-isobutyl-5-(4′-alkoxy-3′-(methylsulfonyl)-[1,1′-biphenyl]-4-yl)-3-(fluoromethyl)-1H-pyrazole derivatives indicate that these compounds could assist in the development of lead compounds to treat microbial infections.