Synthesis of modified Schiff base appended 1,2,4-triazole hybrids scaffolds: Elucidating the in vitro and in silico α-amylase and α-glucosidase inhibitors potential

• Published in: Zeitschrift fur Naturforschung - Section C Journal of Biosciences
• Main Author: Abbasi S.A.; Rahim F.; Hussain R.; Rehman W.; Khan S.; Taha M.; Iqbal T.; Khan Y.; Ali Shah S.A.
• Format: Article
• Language: English
• Published: Walter de Gruyter GmbH 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85198980604&doi=10.1515%2fznc-2024-0073&partnerID=40&md5=c0950164c571dcf808f87e3c39a74674

The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their α-amylase and α-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as 1H-NMR, 13C-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro α-glucosidase and α-amylase inhibitory activities of the synthesized compounds were evaluated in order to determine their potential anti-diabetic properties. All analogues showed varied range of inhibitory activity having IC50 values ranging from 17.09 ± 0.72 to 45.34 ± 0.03 μM (α-amylase) and 16.35 ± 0.42 to 42.31 ± 0.09 μM (α-glucosidase), respectively. Specifically, the compounds 1, 7 and 8 were found to be significantly active with IC50 values of 17.09 ± 0.72, 19.73 ± 0.42, and 23.01 ± 0.04 μM (against α-amylase) and 16.35 ± 0.42, 18.55 ± 0.26, and 20.07 ± 0.02 μM (against α-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC50 values of 13.02 ± 0.11 μM (for α-glucosidase) and 15.04 ± 0.02 μM (for α-amylase), respectively. The structure-activity relationship (SAR) studies were conducted based on differences in substituent patterns at varying position of aryl rings A and B may cause to alter the inhibitory activities of both α-amylase and α-glucosidase enzymes. Additionally, the molecular docking study was carried out to explore the binding interactions possessed by most active analogues with the active sites of targeted α-amylase and α-glucosidase enzymes. © 2024 Walter de Gruyter GmbH, Berlin/Boston 2024.