In-vitro and in-silico assessment of thiazole-thiazolidinone derivatives as selective inhibitors of urease and α-glucosidase

Future Med Chem. 2024 Dec 8:1-10. doi: 10.1080/17568919.2024.2432303. Online ahead of print.

Abstract

Aims: Current research work aims to synthesize hybrid compounds with a thiazole-thiazolidinone structure, as potent inhibitors of urease and α-glucosidase enzymes.

Materials and methods: These compounds were characterize through1HNMR,13CNMR and HREI-MS techniques. These compounds were also evaluated for their potential to inhibit urease and α-glucosidase enzymes for the treatment of urinary tract infections (UTIs) and diabetes treatments. Moreover, molecular docking and ADMET analysis was carried out to confirm biological outcomes.

Results and conclusion: Compounds-4 (IC50 = 1.80 ± 0.80 and 3.61 ± 0.59 μM against urease and α-glucosidase, respectively) exhibited significant effectiveness in inhibiting the activity of both enzymes in comparison to the conventional inhibitors thiourea and acarbose. Molecular docking experiments showed that potent compounds exhibited favorable binding orientations in the active sites of urease and α-glucosidase playing a pivotal role in inhibition profile of these compounds. These compounds were also investigated for their drug likeness and were found with desirable attributes for pharmaceutical development. Based on the findings of this research, these compounds have the potential to be developed into effective anti-diabetic and anti-urease treatments in the future.

Keywords: SAR; Thiazole; molecular docking; thiazolidinone; urease; α-glucosidase.