Bio-Oriented Synthesis of Novel (S)-Flurbiprofen Clubbed Hydrazone Schiff’s Bases for Diabetic Management: In Vitro and In Silico Studies
Aftab Alama, Mumtaz Alia, Najeeb Ur Rehmanb✉, Saeed Mahmud Ullahb c, Sobia Ahsan Halimb, Abdul Latifa, Zainab Zainabd, Ajmal Khanb, Obaid Ullahb, Shujaat Ahmade, Ahmed Al‐Harrasib✉, Manzoor Ahmada✉
- aDepartment of Chemistry, University of Malakand, Dir Lower P.O. Box 18800, Khyber Pakhtunkhwa, Pakistan
- bNatural and Medical Sciences Research Center, University of Nizwa, PC 616, Birkat Al Mauz, Nizwa P.O. Box 33, Oman
- cHusein Ebrahim Jamal Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
- dCollege of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang 050024, China
- eDepartment of Pharmacy, Shaheed Benazir Bhutto University Sheringal, Dir Upper P.O. Box 18800, Khyber Pakhtunkhwa, Pakistan
- ✉Corresponding author
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Abstract
A new series of (S)-flurbiprofen derivatives 4a–4p and 5a–5n were synthesized with different aromatic or aliphatic aldehydes and ketones to produce Schiff’s bases and their structures were confirmed through HR-ESI-MS, 1H, and 13C-NMR spectroscopy. The α-glucosidase inhibitory activities of the newly synthesized compounds were scrutinized, in which six compounds 5k, 4h, 5h, 4d, 4b, and 5i showed potent inhibition in the range of 0.93 to 10.26 µM, respectively, whereas fifteen compounds 4c, 4g, 4i, 4j, 4l, 4m, 4o, 4p, 5c, 5d, 5j, 5l, 5m, 5n and 1 exhibited significant inhibitory activity with IC50 in range of = 11.42 to 48.39 µM. In addition, compounds 5g, 5f, 4k, 4n, and 4f displayed moderate-to-low activities. The modes of binding of all the active compounds were determined through the molecular docking approach, which revealed that two residues, specifically Glu277 and His351 are important in the stabilization of the active compounds in the active site of α-glucosidase. Furthermore, these compounds block the active site with high binding energies (−7.51 to −3.36 kcal/mol) thereby inhibiting the function of the enzyme.