Nimesulide linked acyl thioureas potent carbonic anhydrase I, II and α-glucosidase inhibitors: Design, synthesis and molecular docking studies

Abstract

Molecular hybridization has emerged as an interesting strategy to improve the effectiveness and the scope of well-known drugs. Nimesulide has been used as non-steroidal anti-inflammatory (NSAID) drug for decades and marketed as NIMS™. Nimesulide (3) possesses a nitro group which shows toxic behavior. To enhance the scope and efficacy of the drug nitro group was reduced to amino group (4) and reacted with isothiocyanates of different substituted acid chlorides to afford Nimesulide-acyl thiourea conjugates (5a-n). In the present research work 14 derivatives were synthesized and tested for carbonic anhydrase I, II and α-glucosidase Inhibition assay. These findings established that all new derivatives are more effective α-amylase inhibitors than Acarbose (IC50: 10000 ​nM) used as a positive control α-amylase inhibitor. Among the tested compounds 5g, 5l and 5m were determined to be the best hCA I, II inhibitors.

Keywords

• Nimesulide analogues
• Acyl thiourea
• Molecular hybridization
• Synthetic approaches
• hCA I, II
• α-amylase inhibitor