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-A JOURNAL OF BIOSCIENCES
• Main Authors: Abbasi, Shahzad Ahmad; Rahim, Fazal; Hussain, Rafaqat; Rehman, Wajid; Khan, Shoaib; Taha, Muhammad; Iqbal, Tayyiaba; Khan, Yousaf; Shah, Syed Adnan Ali
• Format: Article; Early Access
• Language: English
• Published: WALTER DE GRUYTER GMBH 2024
• Subjects: Biochemistry & Molecular Biology; Pharmacology & Pharmacy
• Online Access: https://www-webofscience-com.uitm.idm.oclc.org/wos/woscc/full-record/WOS:001266766000001
• ISSN: 0939-5075; 1865-7125
• DOI: 10.1515/znc-2024-0073

The current study involves the synthesis of Schiff bases based on 1,2,4-triazoles skeleton and assessing their alpha-amylase and alpha-glucosidase profile. Furthermore, the precise structures of the synthesized derivatives were elucidated using various spectroscopic methods such as H-1-NMR, C-13-NMR and HREI-MS. Using glimepiride as the reference standard, the in vitro alpha-glucosidase and alpha-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 mu M (alpha-amylase) and 16.35 +/- 0.42 to 42.31 +/- 0.09 mu M (alpha-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 mu M (against alpha-amylase) and 16.35 +/- 0.42, 18.55 +/- 0.26, and 20.07 +/- 0.02 mu M (against alpha-glucosidase) respectively. The obtained results were compared with the Glimepiride reference drug having IC50 values of 13.02 +/- 0.11 mu M (for alpha-glucosidase) and 15.04 +/- 0.02 mu M (for alpha-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 alpha-amylase and alpha-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 alpha-amylase and alpha-glucosidase enzymes.