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

• DOI: 10.1016/j.ejmech.2019.111977
• Publication Date: 2019-12-24T16:45:12Z
• Authors: Mohamed A. Salem; Ahmed Ragab; Ahmed A. Askar; Abeer El-Khalafawy; Abeer H. Makhlouf
• Keywords: Antifungal Agents; Dose-Response Relationship, Drug; Molecular Structure; Topoisomerase Inhibitors; Fungi; Microbial Sensitivity Tests; Gram-Positive Bacteria; 01 natural sciences; Anti-Bacterial Agents; 0104 chemical sciences; 3. Good health; Molecular Docking Simulation; Structure-Activity Relationship; DNA Gyrase; Gram-Negative Bacteria; Immunologic Factors; Spiro Compounds; Arylsulfonates

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.