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. 2022 Sep 15:10:995820.
doi: 10.3389/fchem.2022.995820. eCollection 2022.

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

Yousaf Khan  1 , Shahid Iqbal  2 , Mazloom Shah  3 , Aneela Maalik  1 , Rafaqat Hussain  4 , Shoaib Khan  4 , Imran Khan  4 , Rami Adel Pashameah  5 , Eman Alzahrani  6 , Abd-ElAziem Farouk  7 , Mohammed Issa Alahmdi  8 , Hisham S M Abd-Rabboh  9   10
Affiliations

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

Yousaf Khan et al. Front Chem. .

Abstract

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 IC50 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 (IC50 = 10.30 ± 0.20 µM) (IC50 = 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 IC50 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, -NO2, and -F linked to the phenyl ring had higher inhibitory potentials for -amylase and -glucosidase than scaffolds with -OCH3, -Br, and -CH3 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, 13C-NMR, and HREI-MS mass, were used to explore the correct structure of newly afforded hybrid scaffolds based on quinoline-bearing triazole ring.

Keywords: molecular docking; quinoline; triazole; α-amylase enzymes; α-glucosidase enzymes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Hybridization of the quinoline moiety with a triazole ring.
SCHEME 1
SCHEME 1
Preparation of 7-quinolinyl-based triazole-3-thione derivatives (1d–19d).
FIGURE 2
FIGURE 2
Summary of SAR studies of quinoline-based triazole against α-amylase and α-glucosidase enzymes.
FIGURE 3
FIGURE 3
PLI profile indicates the corresponding surface of α-amylase enzyme and its interactions with fluoro-substituted scaffolds 11 d and 9d.
FIGURE 4
FIGURE 4
PLI profile indicates the corresponding surface of α-glucosidase enzyme and its interactions with fluoro-substituted scaffolds 11 d and 9d.
FIGURE 5
FIGURE 5
PLI profile indicates the corresponding surface of α-amylase and α-glucosidase enzymes and their interactions with the standard acarbose drug.
See this image and copyright information in PMC

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