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; Shahid Iqbal; Mazloom Shah; Aneela Maalik; Rafaqat Hussain; Shoaib Khan; Imran Khan; Rami Adel Pashameah; Eman Alzahrani; Abd-ElAziem Farouk; Mohammed Issa Alahmdi; Hisham S M Abd-Rabboh

doi:10.3389/fchem.2022.995820

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

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

Authors

Affiliations

¹ Department of Chemistry, COMSATS Universityislamabad Campus, Islamabad, Pakistan.
² Department of Chemistry, School of Natural Sciences (SNS), National University of Science and Technology (NUST), Islamabad, Pakistan.
³ Department of Chemistry, Abbottabad University of Science and Technology (AUST), Abbottabad, Pakistan.
⁴ Department of Chemistry, Hazara University, Mansehra, Pakistan.
⁵ Department of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah, Saudi Arabia.
⁶ Department of Chemistry, College of Science, Taif University, Taif, Saudi Arabia.
⁷ Department of Biotechnology College of Science, Taif University, Taif, Saudi Arabia.
⁸ Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.
⁹ Chemistry Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
¹⁰ Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

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.