Synthesis, biological evaluation and molecular modelling of 3-Formyl-6-isopropylchromone derived thiosemicarbazones as α-glucosidase inhibitors

Rabia Basri; Saeed Ullah; Ajmal Khan; Suraj N Mali; Oussama Abchir; Samir Chtita; Ahmed El-Gokha; Parham Taslimi; Ammena Y Binsaleh; Attalla F El-Kott; Ahmed Al-Harrasi; Zahid Shafiq

doi:10.1016/j.bioorg.2023.106739

Synthesis, biological evaluation and molecular modelling of 3-Formyl-6-isopropylchromone derived thiosemicarbazones as α-glucosidase inhibitors

Bioorg Chem. 2023 Oct:139:106739. doi: 10.1016/j.bioorg.2023.106739. Epub 2023 Jul 17.

Authors

Affiliations

¹ Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan.
² Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman.
³ Department of Pharmaceutical Science and Technology, Birla Institute of Technology, Mesra 835215, India.
⁴ Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca B.P 7955, Morocco.
⁵ Chemistry Department, Faculty of Science, Menoufia University Menoufia, Egypt.
⁶ Department of Biotechnology, Faculty of Science, Bartin University, 74100 Bartin, Turkey.
⁷ Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
⁸ Department of Biology, College of Science, King Khalid University, Abha 61421, Saudi Arabia; Department of Zoology, College of Science, Damanhour University, Damanhour 22511, Egypt.
⁹ Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. Electronic address: [email protected].
¹⁰ Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan; Department of Pharmaceutical & Medicinal Chemistry, An der Immenburg 4, D-53121 Bonn, Germany. Electronic address: [email protected].

PMID: 37478545
DOI: 10.1016/j.bioorg.2023.106739

Abstract

Type-2 Diabetes Mellitus (T2DM) is one of the most common metabolic disorders in the world and over the past three decades its incidence has increased drastically. α-Glucosidase inhibitors are used to control the hyperglycemic affect of T2DM. Herein, we report the synthesis, α-glucosidase inhibition, structure activity relationship, pharmacokinetics and docking analysis of various novel chromone based thiosemicarbazones 3(a-r). The derivatives displayed potent activity against α-glucosidase with IC₅₀ in range of 0.11 ± 0.01-79.37 ± 0.71 µM. Among all the synthesized compounds, 3a (IC₅₀ = 0.17 ± 0.026 µM), 3 g (IC₅₀ = 0.11 ± 0.01 µM), 3n (IC₅₀ = 0.55 ± 0.02 µM), and 3p (IC₅₀ = 0.43 ± 0.025 µM) displayed higher inhibitory activity as compared to the standard, acarbose. Moreover, we have developed a statistically significant 2D-QSAR model (R²_tr:0.9693; F: 50.4647 and Q²_LOO:0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of α-glucosidase.

Keywords: Chromene; Diabetes Mellitus; Molecular Docking; Thiosemicarbazones; α-glucosidase inhibition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / drug therapy
Diabetes Mellitus, Type 2* / metabolism
Glycoside Hydrolase Inhibitors / chemistry
Humans
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Thiosemicarbazones* / pharmacology
alpha-Glucosidases / metabolism

Substances

Glycoside Hydrolase Inhibitors
Thiosemicarbazones
alpha-Glucosidases