Synthesis, antimicrobial activity and molecular docking studies of spiroquinoline-indoline-dione and spiropyrazolo-indoline-dione derivatives

Abstract

Spiro[benzo[h]quinoline-7,3′-indoline]diones and spiro[indoline-3,4′-pyrazolo[3,4-b]quinoline]diones were efficiently synthesized via one-pot multi-component reactions under ultrasound-promoted conditions. Spiro[benzo[h]quinoline-7,3′-indoline]dione derivatives were successfully developed by the reaction of isatins, naphthalene-1-amine and 1,3-dicarbonyl compounds. The spiro[indoline-3,4′-pyrazolo[3,4-b]quinoline]dione derivatives were prepared by the reaction of isatins, 5-amino-1-methyl-3-pheylpyrazole, and 1,3-dicarbonyl compounds by using ( ±)-camphor-10-sulfonic acid as a catalyst in H2O/EtOH (3:1 v/v) solvent mixture. The antibacterial activity of the synthesized compounds was evaluated against, Enterococcus faecalis, Staphylococcus aureus and Candida albicans. Compounds 4b, 4h, and 6h showed the strongest antimicrobial activity toward both bacteria. The MIC values of these compounds ranged from 375–3000 µg/mL. The effect of these compounds (4b, 4h, 6h) as a function of applied dose and time was investigated by a kinetic study, and the interaction with these antimicrobial results was simulated by a molecular docking study. We also used the docking approach with Covid-19 since secondary bacterial infections. Docking showed that indoline-quinoline hybrid compounds 4b and 4h exerted the strongest docking binding value against the active sites of 6LU7. In addition, the synthesized compounds had a moderate to good free radical scavenging activity.