2. Academic Validation
  3. Synthesis, in vitro, and in silico studies of 7-fluorochromone based thiosemicarbazones as α-glucosidase inhibitors

Synthesis, in vitro, and in silico studies of 7-fluorochromone based thiosemicarbazones as α-glucosidase inhibitors

  • Sci Rep. 2025 Mar 21;15(1):9816. doi: 10.1038/s41598-025-90156-3.
Faiqa Noreen 1,  Saeed Ullah 2,  Suraj N Mali 3,  Ajmal Khan 4 5,  Javid Hussain 6,  Abdulrahman Alshammari 7,  Norah A Albekairi 7,  Rahul D Jawarkar 8,  Susmita Yadav 9,  Ahmed Al-Harrasi 10,  Zahid Shafiq 11
Affiliations

Affiliations

  • 1 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan.
  • 2 Natural and Medical Sciences Research Centre, University of Nizwa, Birkat Al Mauz, P.O. Box 33, PC, 616, Nizwa, Sultanate of Oman.
  • 3 School of Pharmacy, D.Y. Patil University (Deemed to Be University), Sector 7, Nerul, Navi Mumbai, 400706, India.
  • 4 Natural and Medical Sciences Research Centre, University of Nizwa, Birkat Al Mauz, P.O. Box 33, PC, 616, Nizwa, Sultanate of Oman. ajmalkhan@unizwa.edu.om.
  • 5 Department of Chemical and Biological Engineering, College of Engineering, Korea University, 145 Anam-Ro, Seongbuk-Gu, Seoul, 02841, Republic of Korea. ajmalkhan@unizwa.edu.om.
  • 6 Department of Biological Sciences and Chemistry, University of Nizwa, Nizwa, Oman.
  • 7 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2455, 11451, Riyadh, Saudi Arabia.
  • 8 Department of Medicinal Chemistry and Drug Discovery, Dr. Rajendra Gode Institute of Pharmacy, University Mardi Road, Amravati, 444603, India.
  • 9 Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, 835215, India.
  • 10 Natural and Medical Sciences Research Centre, University of Nizwa, Birkat Al Mauz, P.O. Box 33, PC, 616, Nizwa, Sultanate of Oman. aharrasi@unizwa.edu.om.
  • 11 Institute of Chemical Sciences, Bahauddin Zakariya University, Multan, 60800, Pakistan. zahidshafiq@bzu.edu.pk.
PMID: 40118870 DOI: 10.1038/s41598-025-90156-3
Abstract

Increased blood sugar is a typical manifestation of Type-2 Diabetes Mellitus (T2DM), a metabolic disorder that can be effectively managed with the help of α-glucosidase inhibitors. A range of new chromone based thiosemicarbazone derivatives (3a-t) was synthesized and assessed due to their ability to suppress α-glucosidase in this research. Having IC50 values spanning from 6.40 ± 0.15 to 62.81 ± 0.79 μM, the compounds demonstrated strong inhibitory actions. The compound 3 k showed the most inhibitory effect among all of them, by an IC50 measurement of 6.40 ± 0.15 µM. It was concluded through a structure-activity relationship (SAR) assessment that various substituents on thiosemicarbazone moieties had a significant impact on the differences in α-glucosidase inhibition. Molecular docking experiments provide light on important interactions, including π-π interactions and hydrogen bridges, between compounds and role of the carbothioamide and chromenyl groups in ligand attachment to the critical residues of α-glucosidase. The binding interactions, alignment, stability, and structural arrangement of the prepared molecules in the catalytic pocket of α-glucosidase were explored using in silico strategies such as docking studies, pharmacokinetic analysis, and molecular dynamics simulations. This investigation directed to find compounds with favorable profiles for future progress as potential therapeutic agents for type 2 diabetes. Importantly, when benchmarking against acarbose, the lead candidate showed substantially greater efficacy.

Keywords

7-fluorochromone; ADME; Molecular docking; SAR; Thiosemicarbazones; α-glucosidase inhibition.

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