Synthesis, crystal structure and Hirshfeld Surface analysis of benzamide derivatives of thiourea as potent inhibitors of α-glucosidase in-vitro

Benzamide based structural analogues 1-15 were synthesized, and evaluated for alpha-glucosidase inhibition activity in vitro for the first time. Compounds 1-9 were found to be known, while compounds 10-15 were found to be new. However, to the best of our knowledge we are reporting alpha-glucosidase inhibitory activity of these bezamide derivatives of thiourea for the first time. Compounds 1, 3, 6-8, 10-14 were found to be potent inhibitors of alpha-glucosidase within IC50 range of 20.44-333.41 mu M in comparison to the standard inhibitor, acarbose (IC50 = 875.75 + 2.08 mu M). Mode of the enzyme inhibition was determined on the basis of kinetic studies which demonstrated that compounds 8, and 10 were non-competitive and competitive inhibitors of alpha-glucosidase enzyme, respectively. These compounds were also evaluated for their DPPH radical scavenging activity, and cytotoxicity against 3T3 mouse fibroblast cell lines. All synthesized compounds showed a significant to moderate DPPH radical scavenging activity and appeared to be non-cytotoxic except compound 9 which showed cytotoxicity against 3T3 normal mouse fibroblast cell lines. A single crystal X-ray and Hirshfeld Surface analysis of a representative compound is also presented.

Automated summary

The benzamide-based structural analogues showed potent inhibition of alpha-glucosidase, with most compounds being non-cytotoxic and demonstrating significant DPPH radical scavenging activity. Compound 9 exhibited cytotoxicity against 3T3 normal mouse fibroblast cell lines. Mode of enzyme inhibition was determined for some compounds based on kinetic studies.