Synthesis, in vitro evaluation and molecular docking studies of hybrid 4-quinolinyl bearing 1,3,4-thiadiazole-2-amine as a new inhibitor of α-amylase and α-glucosidase

• Published in: Journal of Molecular Structure
• Main Author: Taha M.; Khan A.A.; Rahim F.; Hayat S.; Imran S.; Iqbal N.; Uddin N.; Khan K.M.; Anouar E.H.; Farooq R.K.; Nawaz M.; Shah S.A.A.
• Format: Article
• Language: English
• Published: Elsevier B.V. 2023
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85149061065&doi=10.1016%2fj.molstruc.2023.135173&partnerID=40&md5=5fb2cb7640406975bc1c70bb2621b487

Synthesized scaffolds (1–19) of 4-quinolinyl based 1,3,4-thiadiazole-2-amine were evaluated in vitro for their α-amylase and α-glucosidase inhibition. All the newly synthesized scaffolds (1–19) were found to illustrate variable degree of inhibitory profile against α-amylase and α-glucosidase enzymes ranging from 1.30 ± 0.05 to 45.60 ± 0.80 µM and 2.70 ± 0.10 µM to 47.60 ± 0.90 µM. Among the series, compounds 2 (IC50 = 2.20 ± 0.10 µM), (IC50 = 8.40 ± 0.20 µM), 3 (IC50 = 4.10 ± 0.10 µM), (IC50 = 5.60 ± 0.10 µM), 4 (IC50 = 1.30 ± 0.05 µM), (IC50 = 2.90 ± 0.10 µM) and 5 (IC50 = 1.90 ± 0.10 µM), (IC50 = 2.70 ± 0.10 µM) were found to be the most potent inhibitors of α-amylase and α-glucosidase enzymes. The elevated inhibitory profile of these scaffolds might be due to presence of flouro and chloro group at different positions of phenyl ring attached to 1,3,4-thiadiazole ring. Various types of spectroscopic techniques such as 1H-, 13C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed scaffolds. To find SAR, molecular docking studies were performed to understand the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data. Molecular dynamics study were performed to further investigate the orientation and binding interaction of the synthesized analogues with active site of α-amylase and α-glucosidase enzyme. ADMET prediction and in silico drug likeness analysis of the synthesized analogues demonstrated that these analogues have satisfactory ADMET profile and drug likeness. © 2023 Elsevier B.V.