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

Autor: Basri R; Institute of Chemical Sciences, Bahauddin Zakariya University, Multan 60800, Pakistan., Ullah S; Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman., Khan A; Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman., Mali SN; Department of Pharmaceutical Science and Technology, Birla Institute of Technology, Mesra 835215, India., Abchir O; Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca B.P 7955, Morocco., Chtita S; Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca B.P 7955, Morocco., El-Gokha A; Chemistry Department, Faculty of Science, Menoufia University Menoufia, Egypt., Taslimi P; Department of Biotechnology, Faculty of Science, Bartin University, 74100 Bartin, Turkey., Binsaleh AY; Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia., El-Kott AF; Department of Biology, College of Science, King Khalid University, Abha 61421, Saudi Arabia; Department of Zoology, College of Science, Damanhour University, Damanhour 22511, Egypt., Al-Harrasi A; Natural and Medical Sciences Research Centre, University of Nizwa, P.O. Box 33, PC 616, Birkat Al Mauz, Nizwa, Sultanate of Oman. Electronic address: aharrasi@unizwa.edu.om., Shafiq Z; 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: zahidshafiq@bzu.edu.pk.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2023 Oct; Vol. 139, pp. 106739. Date of Electronic Publication: 2023 Jul 17.
DOI: 10.1016/j.bioorg.2023.106739
Abstrakt: 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 IC 50 in range of 0.11 ± 0.01-79.37 ± 0.71 µM. Among all the synthesized compounds, 3a (IC 50  = 0.17 ± 0.026 µM), 3 g (IC 50  = 0.11 ± 0.01 µM), 3n (IC 50  = 0.55 ± 0.02 µM), and 3p (IC 50  = 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 (R 2 tr :0.9693; F: 50.4647 and Q 2 LOO :0.9190), which can be used in future to further design potent thiosemicarbazones as inhibitors of α-glucosidase.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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