One-pot synthesis and molecular docking of some new spiropyranindol-2-one derivatives as immunomodulatory agents and in vitro antimicrobial potential with DNA gyrase inhibitor

Abstract

a series of 2-oxospiro[indoline-3,4'-pyran]derivatives 4 and 7 were obtained in good yield under mild conditions from the one-pot reaction of indole-2,3-dione derivatives 1, appropriate methylene active nitriles 2 and β-dicarbonyl compound 3 or 6. The newly synthesized compounds were characterized and evaluated for their in vitro antibacterial, antifungal as well as immunomodulatory activity. According to MIC values, the most potent compounds 4f, 4h, 7a, 7c, 7e, 7f, 7g, 8a, and 8c were evaluated for MBC and displayed high activity to killing pathogens with a good MBC value against norfloxacin as well as investigated against an extended panel of multidrug resistance bacteria (MDRB) and exhibited promising to moderate multidrug resistance activities, compounds 7f showed the much better than norfloxacin with higher potency results. Furthermore, the most potent compounds showed an increase in the intracellular killing activity of neutrophils which confirmed the immunostimulatory power. Eight of the nine active compounds exhibited inhibitory activities with IC₅₀ ranged between (18.07 ± 0.18) to (27.03 ± 0.24) μM stronger than ciprofloxacin (26.43 ± 0.64 μM) for S. aureus DNA gyrase. Molecular docking was performed inside the active site of S. aureus DNA gyrase to predict the binding mode.

Keywords: Antibacterial; Antifungal; DNA-Gyrase inhibition; Immunomodulatory activity; MBC; MIC; Molecular docking; Multidrug-resistant strains; Spiropyranindol-2-one.