Chemo-/regio-selective ultrasound-assisted synthesis of new spirooxindole-pyrrolidines/spirooxindole-pyrrolizines: Synthesis, antimicrobial and antitubercular activities, SAR and in silico studies

Abstract

In an exploration of novel spirooxindole-pyrrolidine/spirooxindole-pyrrolizine-based compounds as antimicrobial and antitubercular agents, we have prepared a new series of pharmacologically privileged substructures, i.e., chalcone-isatin based spirooxindole compounds 12a-j, 13a-e, 14a-d, and 15–16 which were derived by the reaction of various substituted amino acids 11a-d, respectively, substituted chalcone (Me, OMe, Cl) 10a-m and isatins 9a-bvia one-pot three-component [3 + 2] cycloaddition reaction. We also report the SAR, and in silico molecular docking studies of 12a-j, 13a-e, 14a-d, and 15. While compared to the standard drug ampicillin (MIC = 25 µg/mL), compounds 13c, 13e, 14a, and 15 (MIC = 12.5 µg/mL) have shown to be twice as potent against the Bacillus subtilis [BS] bacterial strain. Compounds 12a and 13c (MIC = 25 µg/mL) exhibited equipotent behavior towards ampicillin (MIC = 25 µg/mL), a bacterial strain of B. subtilis [BS]. Compounds 13b (MIC = 3.125 µg/Ml) and 15 (MIC = 1.56 µg/mL) demonstrated strong antitubercular activity in the antitubercular activity assay when compared to the conventional medications Rifampicin (MIC = 0.2 µg/mL) and INH (MIC = 0.1 µg/mL). We also report, for the first time, in vitro antimicrobial activity of some previously reported spiro compounds 12c, 12f and 12 g.