title: A concise synthesis and evaluation of new malonamide derivatives as potential α-glucosidase inhibitors.
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.
authors.affiliation: Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Mohammad Shahidul
authors.initials: MS
authors.lastname: Islam
authors.affiliation: 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.
authors.forename: Assem
authors.initials: A
authors.lastname: Barakat
authors.affiliation: Department of Chemistry, College of Science, King Saud University, PO Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: Abdullah M
authors.initials: AM
authors.lastname: Al-Majid
authors.affiliation: 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.
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ghabbour
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: A F M Motiur
authors.initials: AF
authors.lastname: Rahman
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Kulsoom
authors.initials: K
authors.lastname: Javaid
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Rehan
authors.initials: R
authors.lastname: Imad
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Sammer
authors.initials: S
authors.lastname: Yousuf
authors.affiliation: 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.
authors.forename: M Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D016475:3T3 Cells; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008314:Malonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: D065089:Glycoside Hydrolase Inhibitors; D008314:Malonates; D000520:alpha-Glucosidases; C008314:malonamide
keywords: Cytotoxicity; Diabetes; Malonamide; Michael addition; Nitrogen heterocycles; α-Glucosidase