A concise synthesis and evaluation of new malonamide derivatives as potential α-glucosidase inhibitors

Mohammad Shahidul Islam; Assem Barakat; Abdullah M Al-Majid; Hazem A Ghabbour; A F M Motiur Rahman; Kulsoom Javaid; Rehan Imad; Sammer Yousuf; M Iqbal Choudhary

doi:10.1016/j.bmc.2016.02.037

A concise synthesis and evaluation of new malonamide derivatives as potential α-glucosidase inhibitors

Bioorg Med Chem. 2016 Apr 15;24(8):1675-82. doi: 10.1016/j.bmc.2016.02.037. Epub 2016 Mar 2.

Authors

Mohammad Shahidul Islam¹, Assem Barakat², Abdullah M Al-Majid¹, Hazem A Ghabbour³, A F M Motiur Rahman⁴, Kulsoom Javaid⁵, Rehan Imad⁶, Sammer Yousuf⁵, M Iqbal Choudhary⁷

Affiliations

¹ Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
² Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; Department of Chemistry, Faculty of Science, Alexandria University, PO Box 426, Ibrahimia, 21321 Alexandria, Egypt. Electronic address: ambarakat@ksu.edu.sa.
³ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia; Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
⁴ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
⁵ H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁶ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
⁷ Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia; H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.

PMID: 26972921
DOI: 10.1016/j.bmc.2016.02.037

Abstract

A series of new malonamide derivatives were synthesized by Michael addition reaction of N(1),N(3)-di(pyridin-2-yl)malonamide into α,β-unsaturated ketones mediated by DBU in DCM at ambient temperature. The inhibitory potential of these compounds in vitro, against α-glucosidase enzyme was evaluated. Result showed that most of malonamide derivatives were identified as a potent inhibitors of α-glucosidase enzyme. Among all the compounds, 4K (IC50=11.7 ± 0.5 μM) was found out as the most active one compared to standard drug acarbose (IC50=840 ± 1.73 μM). Further cytotoxicity of 4a-4m were also evaluated against a number of cancer and normal cell lines and interesting results were obtained.

Keywords: Cytotoxicity; Diabetes; Malonamide; Michael addition; Nitrogen heterocycles; α-Glucosidase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3 Cells
Animals
Cell Line, Tumor
Cell Survival / drug effects
Dose-Response Relationship, Drug
Glycoside Hydrolase Inhibitors / chemical synthesis*
Glycoside Hydrolase Inhibitors / chemistry
Glycoside Hydrolase Inhibitors / pharmacology*
Humans
Malonates / chemical synthesis*
Malonates / chemistry
Malonates / pharmacology*
Mice
Models, Molecular
Molecular Structure
Structure-Activity Relationship
alpha-Glucosidases / metabolism*

Substances

Glycoside Hydrolase Inhibitors
Malonates
alpha-Glucosidases
malonamide