α-Glucosidase inhibition assay of galbanic acid and it amide derivatives: New excellent semi-synthetic α-glucosidase inhibitors

Maryam Mohammadi-Khanaposhtani; Mohammad Hosein Sayahi; Rozita Yazzaf; Navid Dastyafteh; Mohammad Halimi; Aida Iraji; Armin Dadgar; Somayeh Mojtabavi; Mohammad Ali Faramarzi; Mahdie Palimi; Roghieh Mirzazadeh; Bagher Larijani; Mohammad-Reza Delnavazi; Mohammad Mahdavi

doi:10.1016/j.bioorg.2024.107580

α-Glucosidase inhibition assay of galbanic acid and it amide derivatives: New excellent semi-synthetic α-glucosidase inhibitors

Bioorg Chem. 2024 Sep:150:107580. doi: 10.1016/j.bioorg.2024.107580. Epub 2024 Jun 20.

Authors

Affiliations

¹ Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
² Department of Chemistry, Payame Noor University, Tehran, Iran; Chemistry Department, College of Science, Shahid Chamran University of Ahvaz, Ahvaz 61357-4-3169, Iran.
³ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Department of Biology, Babol Branch, Islamic Azad University, Babol, Iran.
⁵ Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Central Research Laboratory, Shiraz University of Medical Sciences, Shiraz, Iran; Liosa Pharmed Parseh Company, Shiraz, Iran.
⁶ Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁸ Biochemistry Department, Pasteur Institute of Iran, Tehran, Iran.
⁹ Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: delnavazi@tums.ac.ir.
¹⁰ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: momahdavi@tums.ac.ir.

PMID: 38959646
DOI: 10.1016/j.bioorg.2024.107580

Abstract

α-Glucosidase inhibitory activity of galbanic acid and its new amide derivatives 3a-n were investigated. Galbanic acid and compounds 3a-n showed excellent anti-α-glucosidase activity with IC₅₀ values ranging from 0.3 ± 0.3 μM to 416.0 ± 0.2 μM in comparison to positive control acarbose with IC₅₀ value of = 750.0 ± 5.6. In the kinetic study, the most potent compound 3h demonstrated a competitive mode of inhibition with K_i = 0.57 µM. The interaction of the most potent compound 3h with the α-glucosidase was further elaborated by in vitro Circular dichroism assessment and in silico molecular docking and Molecular dynamics studies. Compound 3h was also non-cytotoxic on human normal cells. In silico study on pharmacokinetics and toxicity profile of the most potent galbanic acid derivatives demonstrated that these compounds are valuable lead compounds for further study in order to achieve new anti-diabetic agents.

Keywords: Amide; Galbanic acid; Semi-synthetic; α-Glucosidase.

MeSH terms

Amides* / chemical synthesis
Amides* / chemistry
Amides* / pharmacology
Dose-Response Relationship, Drug
Glycoside Hydrolase Inhibitors* / chemical synthesis
Glycoside Hydrolase Inhibitors* / chemistry
Glycoside Hydrolase Inhibitors* / pharmacology
Humans
Molecular Docking Simulation*
Molecular Structure
Saccharomyces cerevisiae / enzymology
Structure-Activity Relationship
alpha-Glucosidases* / metabolism

Substances

Glycoside Hydrolase Inhibitors
alpha-Glucosidases
Amides