New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies

Zahid Ali; Wajid Rehman; Liaqat Rasheed; Abdullah Y Alzahrani; Nawab Ali; Rafaqat Hussain; Abdul-Hamid Emwas; Mariusz Jaremko; Magda H Abdellattif

doi:10.1021/acsomega.3c05854

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies

ACS Omega. 2024 Feb 5;9(7):7480-7490. doi: 10.1021/acsomega.3c05854. eCollection 2024 Feb 20.

Authors

Zahid Ali¹, Wajid Rehman¹, Liaqat Rasheed¹, Abdullah Y Alzahrani², Nawab Ali³, Rafaqat Hussain¹, Abdul-Hamid Emwas⁴, Mariusz Jaremko⁵, Magda H Abdellattif⁶

Affiliations

¹ Department of Chemistry, Hazara University, Mansehra 21120, Pakistan.
² Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail, Assir 61421, Saudi Arabia.
³ Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Meilong Road130, Shanghai 200237, PR China.
⁴ Core Laboratories, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
⁵ Biological and Environmental Science and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia.
⁶ Department of Chemistry, Sciences College, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.

Abstract

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1-12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC₅₀ values of 18.10 ± 0.20 to 1.10 ± 0.10 μM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC₅₀ 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 μM by using acarbose as a standard, whose IC₅₀ is 11.50 ± 0.30 μM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.