RESUMO
Herein, we report analogues of s-indacene by the synthesis of novel indolizine derivatives. Using chloroform as an appropriate solvent, sixteen derivatives of pyrazolyl-indolizine (4-19) were prepared by the reaction of 3-(dimethylamino)-1-(1H-pyrrol-2-yl)prop-2-en-1-one with hydrazonoyl chloride derivatives in the presence of triethylamine in good to excellent yields. We used NMR spectra, IR, mass spectrometry, as well as elemental analyses to prove the chemical structures and the purity of the synthesized compounds. Among all tested compounds 5, 9, 13 and 19 had a potent antimicrobial efficiency against Bacillus subtilis, Staphylococcus aureus, Pseudomonas aerginousea, Sallmonella typhemerium, and Candida albicans. Furthermore, a significant increase in lipid peroxidation (LPO) toward the Gram-negative bacteria, Pseudomonas aeruginosa when treated with compound 9 was observed, while compound 13 remarkably increased the cell membrane oxidation of Salmonella typhimurium. Additionally, we utilized docking studies and in silico methods to evaluate the drug-likeness, physicochemical properties, and ADMET profiles of the compounds. The results of the molecular docking simulation revealed that the synthesized compounds displayed decreased binding energy when interacting with the active sites of important enzymes, including Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of S. typhimurium, and Gyrase B of B. subtilis.
