Multicomponent synthesis, biological evaluation and molecular docking of new spiro-oxindole derivatives

Abstract

A new series of spiro-oxindoles that were identified based upon their ability to inhibit methionine tRNA synthase (PDB ID: 1PFV) and glucosamine-6-phosphate synthase (PDB ID: 1JXA) enzymes in virtual screening was synthesized by a three-component 1,3-dipolar cycloaddition method. The reaction proceeds through the formation of azomethine ylides generated in situ by the decarboxylative condensation of isatin and amino acids with dipolarophile chalcones. These compounds are active against Staphylococcus aureus, Escherichia coli, Aspergillus niger and Aspergillus flavus, supporting the in silico screening. In addition, their antitubercular activity was assessed using the MABA method. The compounds 3′-[(4-fluorophenyl)carbonyl]-4′-phenylspiro[indole-3,2′-pyrrolidin]-2(1H)-one 3a, 4′-(4-bromophenyl)-3′-[(4-fluorophenyl)carbonyl]-5′-(hydroxymethyl) spiro[indole-3,2′-pyrrolidin]-2(1H)-one 3e and 4′-(4-chlorophenyl)-3′-[(4-fluorophenyl)carbonyl]-5′-(2-methylpropyl)spiro[indole-3,2′-pyrrolidin]-2(1H)-one 3g are potent molecules with MIC of 0.8 μg/mL. In the DPPH radical scavenging assay, compounds 4′-(4-chlorophenyl)-3′-[(4-fluorophenyl)carbonyl]spiro[indole-3,2′-pyrrolidin]-2(1H)-one 3b, 4′-(4-chlorophenyl)-3′-[(4-fluorophenyl)carbonyl]-5′-(hydroxymethyl)spiro[indole-3,2′-pyrrolidin]-2(1H)-one 3d and 4′-(4-bromophenyl)-3′-[(4-fluorophenyl)carbonyl]-5′-(hydroxymethyl)spiro[indole-3,2′-pyrrolidin]-2(1H)-one 3e exhibited significant radical scavenging capacity. Keywords: Chalcone, Spiro-oxindole, Azomethine ylide, Antimicrobial activity, Molecular docking