Design and synthesis of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids as new anti-diabetic agents: in vitro α-glucosidase inhibition, kinetic and docking studies

• Published in: Molecular diversity 2021-05, Vol.25 (2), p.877-888
• Main Authors: Asgari, Mohammad Sadegh, Mohammadi-Khanaposhtani, Maryam, Sharafi, Zeinab, Faramarzi, Mohammad Ali, Rastegar, Hossein, Nasli Esfahani, Ensieh, Bandarian, Fatemeh, Ranjbar Rashidi, Parviz, Rahimi, Rahmatollah, Biglar, Mahmood, Mahdavi, Mohammad, Larijani, Bagher
• Format: Article
• Language: English
• Subjects: Antidiabetics; Biochemistry; Biomedical and Life Sciences; Life Sciences; Organic Chemistry; Original Article; Pharmacy; Polymer Sciences
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-020-10072-8

Fourteen novel 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a – n were synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1H-imidazole and various benzyl azides. The synthesized compounds 8a – n were evaluated against yeast α-glucosidase, and all these compounds exhibited excellent inhibitory activity (IC 50 values in the range of 85.6 ± 0.4–231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC 50  = 750.0 μM). Among them, 4,5-diphenyl-imidazol-1,2,3-triazoles possessing 2-chloro and 2-bromo-benzyl moieties (compounds 8g and 8i ) demonstrated the most potent inhibitory activities toward α-glucosidase. The kinetic study of the compound 8g revealed that this compound inhibited α-glucosidase in a competitive mode. Furthermore, docking calculations of these compounds were performed to predict the interaction mode of the synthesized compounds in the active site of α-glucosidase. Graphic abstract A novel series of 4,5-diphenyl-imidazol-1,2,3-triazole hybrids 8a – n was synthesized with good yields by performing click reaction between the 4,5-diphenyl-2-(prop-2-yn-1-ylthio)-1Himidazole and various benzyl azides. The synthesized compounds 8a – n were evaluated against yeast α-glucosidase and all these compounds exhibited excellent inhibitory activity (IC50 values in the range of 85.6 ± 0.4-231.4 ± 1.0 μM), even much more potent than standard drug acarbose (IC50 = 750.0 μM).