Microwave assisted synthesis of chalcone and its polycyclic heterocyclic analogues as promising antibacterial agents: In vitro, in silico and DFT studies

Abstract Microwave assisted condensation of 3-acetyl-2,5-dimethylthiophene ( 1 ) and 9-ethyl-9 H -carbazole-3-carbaldehyde ( 2 ) gave 1-(2,5-Dimethylthiophen-3-yl)-3-(9-ethyl-9 H -carbazol-3-yl)prop-2-en-1-one (chalcone) ( 1.1 ) which was cyclized to pyrazoline ( 1.2, 1.3 ), and pyrimidine ( 1.4, 1.5 ) derivatives. All the synthesized compounds were subjected to antibacterial activity evaluation using two Gram + ve and two Gram-ve bacterial strains and were tested for any possible toxic effect to the mammalian cells. Density functional theory was used to understand the electronic structure of the studied molecules. All the molecules were modeled and optimized using B3LYP/6-311 + G** level of theory. The relationship between activities and Frontier Molecular orbital (HOMO and LUMO orbitals) of the compounds is also discussed. Docking studies were also performed. The observed results revealed that the pyrazoline skeleton is a promising lead structure, which displays higher in vitro antibacterial efficacy, probably by interacting and inhibiting the glucosamine-6-phosphate synthetase enzyme (GlmS). Theoretical calculations are in good agreement with the in vitro and in silico findings.