Affiliation:
1. Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia
3. Center for Artificial Intelligence in Precision Medicines, King Abdulaziz University, Jeddah 21589, Saudi Arabia
4. Department of Chemistry, Preparatory Year Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia
5. Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt
Abstract
Diabetes is a chronic fast-growing metabolic disorder that is characterized by high blood glucose levels. Tagetes minuta L. has been used as a traditional remedy for various illnesses for many years, and, furthermore, its oil is used in the perfume and flavor industries. T. minuta contains various metabolites, such as flavonoids, thiophenes, terpenes, sterols, and phenolics, with varied bioactivities. Flavonoids can inhibit carbohydrate-digesting enzymes, such as alpha-amylase, which is a convenient dietary strategy for controlling hyperglycemia. In the current investigation, the isolated flavonoids quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside), quercetagetin-7-O-β-D-glucopyranoside, quercetagetin-6-O-β-D-glucopyranoside, minutaside A, patuletin-7-O-β-D-glucopyranoside, quercetagetin-7-methoxy-6-O-β-D-glucopyranoside, tagenols A and B, quercetagetin-3,7-dimethoxy-6-O-β-D-glucopyranoside, patuletin, quercetin-3,6-dimethyl ether, and quercetin-3-methyl ether from T. minuta were assessed for their alpha-amylase inhibition (AAI) efficacy using an in vitro assay, as well as molecular docking, dynamics simulation, and ADMET analyses. Our findings show that quercetagetin-6-O-(6-O-caffeoyl-β-D-glucopyranoside) (1), quercetagetin-7-O-β-D-glucopyranoside (2), quercetagetin-6-O-β-D-glucopyranoside (3), minutaside A (4), patuletin-7-O-β-D-glucopyranoside (5), and quercetagetin-7-methoxy-6-O-β-D-glucopyranoside (6) had a notable AAI capacity (IC50s ranged from 7.8 to 10.1 μM) compared to acarbose (IC50 7.1 μM). Furthermore, these compounds with the highest binding affinity among the tested flavonoids revealed high docking scores for AA (ranging from −12.171 to 13.882 kcal/mol) compared to that of acarbose (−14.668 kcal/mol). In MDS, these compounds were observed to show maximum stability and the greatest binding free energy, suggesting that they may contend with native ligands. In addition, the ADMET analysis showed that these active compounds had a broad span of drug-like, pharmacokinetic, and physicochemical features and did not possess any considerable undesired effects. The current results suggest the potential of these metabolites as AAI candidates. However, further in vivo and mechanistic studies are warranted to specify the efficacy of these metabolites.
Funder
Institutional Fund Projects
Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis