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New Hybrid Scaffolds based on Hydrazinyl Thiazole Substituted Coumarin; As Novel Leads of Dual Potential; In Vitro α-Amylase Inhibitory and Antioxidant (DPPH and ABTS Radical Scavenging) Activities

[ Vol. 15 , Issue. 1 ]

Author(s):

Uzma Salar, Khalid Mohammed Khan*, Sridevi Chigurupati, Shazia Syed, Shantini Vijayabalan, Abdul Wadood, Muhammad Riaz, Mehreen Ghufran and Shahnaz Perveen   Pages 87 - 101 ( 15 )

Abstract:


Background: Despite of many side effects associated, there are many drugs which are being clinically used for the treatment of type-II diabetes mellitus (DM). In this scenario, there is still need to develop new therapeutic agents with more efficacy and less side effects. By keeping in mind the diverse spectrum of biological potential associated with coumarin and thiazole, a hybrid class based on these two heterocycles was synthesized.

Method: Hydrazinyl thiazole substituted coumarins 4-20 were synthesized via two step reaction. First step was the acid catalyzed reaction of 3-formyl/acetyl coumarin derivatives with thiosemicarbazide to form thiosemicarbazone intermediates 1-3, followed by the reaction with different phenacyl bromides to afford products 4-20. All the synthetic analogs 4-20 were characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemical assignment of the iminic double bond was carried out by the NOESY experiments. Elemental analysis was found in agreement with the calculated values.

Results: Compounds 4-20 were screened for α-amylase inhibitory activity and showed good activity in the range of IC50 = 1.829 ± 0.102-3.37 ± 0.17 µM as compared to standard acarbose (IC50 = 1.819 ± 0.19 µM). Compounds were also investigated for their DPPH and ABTS radical scavenging activities and displayed good radical scavenging potential. In addition to that molecular modelling study was conducted on all compounds to investigate the interaction details of compounds 4-20 (ligands) with active site (receptor) of enzyme.

Conclusion: The newly identified hybrid class may serve as potential lead candidates for the management of diabetes mellitus.

Keywords:

Coumarin, hydrazinyl thiazole, in vitro; in silico, a-amylase activity, DPPH, ABTS.

Affiliation:

H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, 08100 Bedong, Kedah, Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University, Mardan, PCSIR Laboratories Complex, Karachi, Shahrah-e-Dr. SalimuzzamanSiddiqui, Karachi-75280



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