Synthesis, enzyme inhibitory kinetics and computational studies of novel 1-(2-(4-isobutylphenyl) propanoyl)-3-arylthioureas as Jack bean urease inhibitors

Abstract

In this article synthesis of a novel 1-(2-(4-isobutylphenyl)propanoyl)-3-arylthioureas (4a-j) as jack bean urease inhibitors has been described. Freshly prepared 2-(4-isobutylphenyl) propanoyl isothiocyanate was treated with substituted aromatic anilines in one pot using anhydrous acetone. The compounds 4e, 4h and 4j showed IC₅₀ values 0.0086nM, 0.0081nM and 0.0094nM respectively. The enzyme inhibitory kinetics results showed that compound 4h inhibit the enzyme competitively while derivatives 4e and 4j are the mixed type inhibitors. The compound 4h reversibly binds the urease enzyme showing Ki value 0.0012nM. The Ki values for 4e and 4j are 0.0025nM and 0.003nM respectively. The antioxidant activity results reflected that compounds 4b, 4i and 4j showed excellent radical scavenging activity. Moreover, the cytotoxic activity of the target compounds was evaluated using brine shrimp assay and it was found that all of the synthesized compounds exhibited no cytotoxic effects to brine shrimps. The computational molecular docking and molecular dynamic simulation of title compounds was also performed and results showed that the wet lab findings are in good agreement to the dry lab results. Based upon our results it is proposed that compound 4h may act as a lead candidate to design the clinically useful urease inhibitors.

The present work reports the synthesis, enzyme inhibitory kinetics and computational studies of some novel aryl thioureas as jack bean urease inhibitors.

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