Novel N -methylsulfonyl-indole derivatives: biological activity and COX-2/5-LOX inhibitory effect with improved gastro protective profile and reduced cardio vascular risks.

Three novel series of -methylsulfonylindole derivatives , and were synthesised. Different biological activities of the synthesised compounds were studied. Antimicrobial activity showed that, compounds , and had selective antibacterial activity against the Gram-negative bacteria, . The anti-oxidant activity of the synthesised compounds was evaluated by DPPH radical scavenging activity. anti-inflammatory activity was estimated. Compounds , , , and showed the highest anti-inflammatory activity. The COX-1, COX-2 and 5-LOX inhibitory activities were measured using enzyme immune assay (EIA) kits. Due to the dual COX-2/5-LOX inhibitory activity of compound , its cardiovascular profile was determined by measuring cardiac biomarkers (LDH, CK-MB, and Tn-I). Besides, the histopathological study of the heart muscle and stomach were examined for the most active COX-2 inhibitors and . Finally, a molecular modelling study and pharmacokinetic properties were obtained using different computational methods.