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Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers

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Abstract

A series of 3-substituted and 3,5-disubstituted rhodanine-based derivatives were synthesized from 3-aminorhodanine and examined for α-amylase inhibitory, DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activities in vitro. These derivatives displayed significant α-amylase inhibitory potential with IC50 values of 11.01–56.04 µM in comparison to standard acarbose (IC50 = 9.08 ± 0.07 µM). Especially, compounds 7 (IC50 = 11.01 ± 0.07 µM) and 8 (IC50 = 12.01 ± 0.07 µM) showed highest α-amylase inhibitory activities among the whole series. In addition to α-amylase inhibitory activity, all compounds also demonstrated significant scavenging activities against DPPH and ABTS radicals, with IC50 values ranging from 12.24 to 57.33 and 13.29–59.09 µM, respectively, as compared to the standard ascorbic acid (IC50 = 15.08 ± 0.03 µM for DPPH; IC50 = 16.09 ± 0.17 µM for ABTS). These findings reveal that the nature and position of the substituents on the phenyl ring(s) are crucial for variation in the activities. The structure-activity relationship (SAR) revealed that the compounds bearing an electron-withdrawing group (EWG) at para substitution possessed the highest activity. In kinetic studies, only the km value was changed, with no observed changes in Vmax, indicating a competitive inhibition. Molecular docking studies revealed important interactions between compounds and the α-amylase active pocket. Further advanced research needs to perform on the identified compounds in order to obtain potential antidiabetic agents.

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Acknowledgements

Dr. Samuel Attah Egu is thankful to The World Academy of Sciences, Trieste, Italy, for awarding a prestigious Fellowship for the year 2019–2020 under the TWAS-ICCBS Postdoctoral Fellowship Programme. The authors also acknowledge the financial support of the Pakistan Academy of Science, 3-Constitution Avenue, G-5/2, Islamabad-44000, Pakistan, under PAS Project No. 111.

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Authors and Affiliations

  1. Department of Pure and Industrial Chemistry, Kogi State University, Anyigba, Kogi State, Nigeria

    Samuel Attah Egu

  2. International Center for Chemical and Biological Sciences, H. E. J. Research Institute of Chemistry, University of Karachi, Karachi, 75270, Pakistan

    Samuel Attah Egu, Irfan Ali & Khalid Mohammed Khan

  3. Department of Clinical Pharmacy, Institute for Research and Medical Consultations [IRMC], Imam Abdulrahman Bin Faisal University, P.O. Box 31441, Dammam, Kingdom of Saudi Arabia

    Khalid Mohammed Khan & Muhammad Taha

  4. Pakistan Academy of Science, 3-Constitution Avenue, G-5/2, Islamabad, 44000, Pakistan

    Khalid Mohammed Khan

  5. Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 52571, Kingdom of Saudi Arabia

    Sridevi Chigurupati & Suliman A. Almahmoud

  6. Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan

    Urooj Qureshi, Uzma Salar & Zaheer Ul-Haq

  7. Department of Medical Laboratory Science, Fakeeh College for Medical Sciences, Jeddah, 21461, Kingdom of Saudi Arabia

    Shatha Ghazi Felemban

  8. Department of Chemistry, University of Karachi, Karachi, 75270, Pakistan

    Mohsin Ali

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  1. Samuel Attah Egu
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Egu, S.A., Ali, I., Khan, K.M. et al. Rhodanine-benzamides as potential hits for α-amylase enzyme inhibitors and radical (DPPH and ABTS) scavengers. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10813-z

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