Ultrasound assisted MK-10 catalyzed new benzimidazole bejeweled quinoline molecular hybrids: Facile synthesis, SAR, molecular modelling and biological evaluation as free radical scavengers and antiinflammatory agents

Abstract

A green, highly efficient ultrasound promoted synthesis of 2‑chloro-3-(5-substituted benzimidazol-2-yl)quinolines, 3(a-o) has been developed at room temperature using MK-10 as catalyst in moderate to good yields within shorter reaction times. Further, the MK-10 catalyst is recovered and reused up to 4 cycles without any loss of catalytic activity. All the synthesized compounds were successfully characterized by using 1H NMR, 13C NMR and LC-MS spectral analysis. The compounds 3(a-o) were evaluated for its antioxidant and anti-inflammatory activities. Antioxidant results of the compounds 3e, 3i and 3j were showing good IC50 values in DPPH, H2O2 and lipid peroxidation methods, out of which compound 3j exhibited highest antioxidant efficacy on par with standard ascorbic acid. Compounds 3j and 3i manifested good anti-inflammatory efficacy with percentage inhibition of 80.16 ± 0.07 and 72.28 ± 0.64 for membrane stabilization method, 85.30 ± 0.06 and 78.64 ± 0.14 for proteinase inhibitory method. To validate the anti-inflammatory results of the compounds 3e, 3i and 3j molecular modeling simulations were performed. The results clearly demonstrated that compound 3j possess strong binding affinity towards 4-COX receptor showing a binding energy of -10.6 kcal/mol similar to that of standard Aceclofenac (-10.8 kcal/mol) and higher than standard Etodolac (-8.8 kcal/mol) while the compounds 3i and 3e exhibited moderate binding affinity.