An effort to find new α-amylase inhibitors as potent antidiabetics compounds based on indole-based-thiadiazole analogs

Abstract

Inhibition of α-amylase enzyme is of key significance for the therapy of diabetes mellitus (DM). Numerous indole-based compounds have earlier been described for broad range of bioactivities. From our previous study, we knew that indole and thiadiazole are potent inhibitors of diabetics II. We design the hybrid molecules of them and synthesized 18 derivatives of indole-based-thiadiazole (1–18). All synthesized compounds were characterized using different spectroscopic methods and evaluated for their α-amylase inhibitory activities. All synthetic compounds, except 4, 13, 15 and 16, were found to be strongly active (IC₅₀ values in the range of 0.80 ± 0.05 − 9.30 ± 0.20 µM) than the standard drug, acarbose (IC₅₀ = 11.70 ± 0.10 µM). Nevertheless, compound 18 was found to be inactive. The modes of binding interactions of five most active compounds 2, 3, 5, 10 and 17 were also studies through molecular docking study. In brief, current study identifies a novel class of α-amylase inhibitors which can be further studied for the treatment of hyperglycemia and obesity.

Communicated by Ramaswamy H. Sarma

Keywords:

• Thiadiazole
• α-amylase inhibition
• molecular docking
• structure–activity relationship
• antihyperglycemic

Acknowledgements

Authors would like to acknowledge financial support for this study by Deanship of Scientific Research, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia, under Project No. 2019-211-IRMC.

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

The author(s) reported there is funding under Project No. 2019-211-IRMC associated with the work featured in this article.