Design, Synthesis, In Silico Testing, and In Vitro Evaluation of Thiazolidinone-Based Benzothiazole Derivatives as Inhibitors of α-Amylase and α-Glucosidase

Shoaib Khan; Shahid Iqbal; Marwa Khan; Wajid Rehman; Mazloom Shah; Rafaqat Hussain; Liaqat Rasheed; Yousaf Khan; Ayed A Dera; Rami Adel Pashameah; Eman Alzahrani; Abd-ElAziem Farouk

doi:10.3390/ph15101164

Design, Synthesis, In Silico Testing, and In Vitro Evaluation of Thiazolidinone-Based Benzothiazole Derivatives as Inhibitors of α-Amylase and α-Glucosidase

Pharmaceuticals (Basel). 2022 Sep 20;15(10):1164. doi: 10.3390/ph15101164.

Authors

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
² Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), H-12, Islamabad 46000, Pakistan.
³ Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad 22500, Pakistan.
⁴ Department of Chemistry, COMSATS University Islamabad Campus, Islamabad 45550, Pakistan.
⁵ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia.
⁶ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah 24230, Saudi Arabia.
⁷ Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁸ Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

In this study, a stepwise reaction afforded thiazolidinone-based benzothiazole derivatives 1-15, and the synthesized derivatives were then screened for biological significance and found to be the leading candidates against α-amylase and α-glucosidase enzymes. Almost all derivatives showed excellent to good activity ranging against α-amylase, IC50 = 2.10 ± 0.70 to 37.50 ± 0.70 μM, and α-glucosidase, IC50 = 3.20 ± 0.05 to 39.40 ± 0.80 μM. Some analogues such as 4 (2.40 ± 0.70 and 3.50 ± 0.70 μM), 5 (2.30 ± 0.05 and 4.80 ± 0.10 μM), and 6 (2.10 ± 0.70 and 3.20 ± 0.70 μM) were found with folds better activity than that of the standard drug acarbose (9.10 ± 0.10 and 10.70 ± 0.10 μM), respectively. Moreover, the structure-activity relationship (SAR) has been established for all compounds. A molecular docking study has been carried out to explore the binding interactions against α-amylase and α-glucosidase enzymes.

Keywords: SAR; benzothiazole; molecular docking; synthesis; thiazolidinone; α-amylase and α-glucosidase enzymes.

Grants and funding

22UQU4320141DSR48/Umm al-Qura University