New quinoline-based triazole hybrid analogs as effective inhibitors of α-amylase and α-glucosidase: Preparation, in vitro evaluation, and molecular docking along with in silico studies

The 7-quinolinyl-bearing triazole analogs were synthesized (1d–19d) and further assessed in vitro for their inhibitory profile against α-amylase andα-glucosidase. The entire analogs showed a diverse range of activities having IC(50) values between 0.80 ± 0.05 µM to 40.20 ± 0.70 µM (α-amylase) and 1.20 ± 0.10 µM to 43.30 ± 0.80 µM (α-glucosidase) under the positive control of acarbose (IC(50) = 10.30 ± 0.20 µM) (IC(50) = 9.80 ± 0.20 µM) as the standard drug. Among the synthesized scaffolds, seven scaffolds 12d, 10d, 8d, 9d, 11d, 5d, and 14d showed excellent α-amylase and α-glucosidase inhibitory potentials with IC(50) values of 4.30 ± 0.10, 2.10 ± 0.10, 1.80 ± 0.10, 1.50 ± 0.10, 0.80 ± 0.05, 5.30 ± 0.20, and 6.40 ± 0.30 µM (against α-amylase) and 3.30 ± 0.10, 2.40 ± 0.10, 1.20 ± 0.10, 1.90 ± 0.10, 8.80 ± 0.20, 7.30 ± 0.40, and 5.50 ± 0.10 µM (against α-glucosidase), respectively, while the remaining 12 scaffolds 19d, 8d, 17d, 16d, 15d, 7d, 4d, 3d, 1d, 2d, 13d and 6 d showed less α-amylase and α-glucosidase inhibitory potentials than standard acarbose but still found to be active. Structure–activity connection studies also showed that scaffolds with electron-withdrawing groups like -Cl, -NO(2), and -F linked to the phenyl ring had higher inhibitory potentials for -amylase and -glucosidase than scaffolds with -OCH(3), -Br, and -CH(3) moieties. In order to better understand their binding sites, the powerful scaffolds 11d and 9d were also subjected to molecular docking studies. The results showed that these powerful analogs provide a number of important interactions with the active sites of both of these targeted enzymes, including conventional hydrogen bonding, pi–pi stacking, pi–sulfur, pi–anion, pi–pi, pi–sigma, T-shaped, and halogen (fluorine). Furthermore, various techniques (spectroscopic), including 1H, (13)C-NMR, and HREI-MS mass, were used to explore the correct structure of newly afforded hybrid scaffolds based on quinoline-bearing triazole ring.