Flurbiprofen derivatives as novel α-amylase inhibitors: Biology-oriented drug synthesis (BIODS), in vitro, and in silico evaluation
Momin Khana b✉, Aftab Alamb, Khalid Mohammed Khanc d e✉, Uzma Salarc, Sridevi Chigurupatif, Abdul Wadoodg, Farman Alic, Jahidul Islam Mohammadh, Muhammad Suleman Riazg, Shahnaz Perveeni
- aDepartment of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan. Electronic address: mominkhan@awkum.edu.pk
- bDepartment of Chemistry, Abdul Wali Khan University, Mardan 23200, Pakistan
- cH.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
- dDepartment of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia. Electronic address: khalid.khan@iccs.edu
- eDepartment of Clinical Pharmacy, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia
- fDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Malaysia
- gDepartment of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Pakistan
- hDepartment of Pharmacology, Faculty of Medicine, Cyberjaya University College of Medical Sciences, CUCMS, Cyberjaya 63000, Malaysia
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Abstract
Novel derivatives of flurbiprofen 1-18 including flurbiprofen hydrazide 1, substituted aroyl hydrazides 2-9, 2-mercapto oxadiazole derivative 10, phenacyl substituted 2-mercapto oxadiazole derivatives 11-15, and benzyl substituted 2-mercapto oxadiazole derivatives 16-18 were synthesized and characterized by EI-MS, 1 H and 13 C NMR spectroscopic techniques. All derivatives 1-18 were screened for α-amylase inhibitory activity and demonstrated a varying degree of potential ranging from IC 50 = 1.04 ± 0.3 to 2.41 ± 0.09 µM as compared to the standard acarbose (IC 50 = 0.9 ± 0.04 µM). Out of eighteen compounds, derivatives 2 (IC 50 = 1.69 ± 0.1 µM), 3 (IC 50 = 1.04 ± 0.3 µM), 9 (IC 50 = 1.25 ± 1.05 µM), and 13 (IC 50 = 1.6 ± 0.18 µM) found to be excellent inhibitors while rest of the compounds demonstrated comparable inhibition potential. A limited structure-activity relationship (SAR) was established by looking at the varying structural features of the library. In addition to that, in silico study was conducted to understand the binding interactions of the compounds (ligands) with the active site of α-amylase enzyme.