Diversity-oriented synthesis of 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids as antimicrobial agents and DFT study

Abstract

Abstract A straightforward and high yielding synthetic approach is employed to synthesize the novel 1H-1,2,3-triazole tethered pyrazolo[5,1-b]quinazoline hybrids 7(a-t) as new antimicrobial agents with two pharmacophore in the effective two step synthesis. The first step is the four component one-pot synthesis of highly functionalized pyrazolo[5,1-b]quinazolines 5(a-j) catalysed by TBAB, with the advantages of an environmentally benign reaction, high yielding, quick reaction time, and operational simplicity. In the subsequent stage, CuSO4/NaAsc system was employed to synthesize the 1H-1,2,3-triazole tethered pyrazolo[1,5-b]quinazoline hybrids as 1H-1,2,3-triazoles are the structures of great diversity and importance in diverse therapeutics containing numerous biological activities. The geometry optimizations have been studied to support the possible mechanism through density functional theory (DFT) calculations using B3LYP/6–31 + G (d,p) basis set. The antimicrobial activity of all the synthesized hybrid compounds have been preliminary tested using the broth dilution technique against two gram-positive and two gram-negative bacterial strains as well as two fungal strains. In comparison to standard drugs, the majority of compounds exhibited good to moderate activity. Among the all the compounds, 7a (MIC 12.5 µg/mL) against Pseudomonas aeruginosa, 7j (MIC 50 µg/mL) against Bacillus subtilis and Rhizopus oryzae and 7t (MIC 50 µg/mL) against Aspergillus parasiticus have remarkable antimicrobial potency as compared to standard drug.