Design, synthesis and bio-evaluation of indolin-2-ones as potential antidiabetic agents

Author:

Asuquo Itohowo Gabriel12,Solangi Mehwish1ORCID,Khan Khalid Mohammed13ORCID,Chigurupati Sridevi4,Otuokere Ifeanyi Edozie2,Ekuma Francis Kalu2,Salar Uzma5ORCID,Felemban Shatha Ghazi6,Rehman Ashfaq Ur7,Wadood Abdul7,Taha Muhammad3ORCID

Affiliation:

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

2. Department of Chemistry, Michael Okpara University of Agriculture, Umudike, 440101, Abia State, Nigeria

3. Department of Clinical Pharmacy, Institute for Research & Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, PO Box 31441, Dammam, Saudi Arabia

4. Department of Medicinal Chemistry & Pharmacognosy, College of Pharmacy, Qassim University, Buraydah, 52571, Saudi Arabia

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

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

7. Department of Biochemistry, Shankar Campus, Abdul Wali Khan University, Mardan, 23200, Khyber Pakhtunkhwa, Pakistan

Abstract

Background: Diabetes mellitus is a serious global health concern, and this is expected to impact more than 300 million people by 2025. The current study focuses on identifying substituted indolin-2-one-based inhibitors for two indispensable drug targets, α-amylase and α-glucosidase. Methods: The structures of synthetic compounds were confirmed by spectroscopic techniques and evaluated for enzyme inhibition activities. Kinetic and in silico studies were also performed. Results: All compounds exhibited good-to-moderate inhibitory potential. Most importantly, compounds 1, 2, 6, 16 and 17 were identified as potent α-glucosidase inhibitors (IC50 = 9.15 ± 0.12–13.74 ± 0.12 μM). Conclusion: This study identified that these synthetic compounds might serve as potential lead molecules for antidiabetic agents.

Funder

Sindh Higher Education Commission Pakistan

The World Academy of Sciences (TWAS) and International Center for Chemical and Biological Sciences, University of Karachi, Pakistan

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

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