p-TSA.H2O mediated one-pot, multi-component synthesis of isatin derived imidazoles as dual-purpose drugs against inflammation and cancer.

A novel one-pot multicomponent reaction was performed to synthesize different imidazole and benzotriazole (BTA) isatin-based medicinally important compounds using (p-TSA·H2O) as an economical and operative acid catalyst. The yield of the products was found to be up to a maximum of 92% when using this catalyst. Antioxidant, anti-breast cancer and anti-inflammatory activities of these 13 isatin-based derivatives (named as 5a-m) were assessed. The inhibitory effects of these compounds were tested in vitro against cyclooxygenase-2 (COX-2, an enzyme responsible for inflammation) and phosphoinositide-3 kinase (PI3K, a key enzyme in breast cancer). "Among the 13 isatin-based Imidazole derivatives, five compounds (5a, 5d, 5f, 5 k and 5l) were found to exhibit anti-inflammatory as well as anti-cancer activity, which was validated using HRBC stabilization assay (to show anti-inflammatory activity) and cytotoxicity in MCF-7 (breast cancer cell line) to provide proof for anti-cancer property of the compounds". The molecular interactions between the two enzymes were probed using molecular docking. Structure-Activity Relationship (SAR) and ADMET prediction results were also useful to screen the most effective imidazole derivatives and to establish them as putative COX-2 inhibitors/anti-inflammatory drugs. These selected compounds which showed appreciable activity against COX-2 and PI3K are promising drug candidates for the treatment of breast cancer and inflammation which is often associated with breast cancer pathophysiology.