title: Synthesis, in vitro biological activities and in silico study of dihydropyrimidines derivatives.
abstract: We describe here the synthesis of dihydropyrimidines derivatives 3a-p, and evaluation of their α-glucosidase enzyme inhibition activities. Compounds 3b (IC50=62.4±1.5 μM), 3c (IC50=25.3±1.26 μM), 3d (IC50=12.4±0.15 μM), 3e (IC50=22.9±0.25 μM), 3g (IC50=23.8±0.17 μM), 3h (IC50=163.3±5.1 μM), 3i (IC50=30.6±0.6 μM), 3m (IC50=26.4±0.34 μM), and 3o (IC50=136.1±6.63 μM) were found to be potent α-glucosidase inhibitors in comparison to the standard drug acarbose (IC50=840±1.73 μM). The compounds were also evaluated for their in vitro cytotoxic activity against PC-3, HeLa, and MCF-3 cancer cell lines, and 3T3 mouse fibroblast cell line. All compounds were found to be non cytotoxic, except compounds 3f and 3m (IC50=17.79±0.66-20.44±0.30 μM), which showed a weak cytotoxic activity against the HeLa, and 3T3 cell lines. In molecular docking simulation study, all the compounds were docked into the active site of the predicted homology model of α-glucosidase enzyme. From the docking result, it was observed that most of the synthesized compounds showed interaction through carbonyl oxygen atom and polar phenyl ring with active site residues of the enzyme.
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. Electronic address: shahid.10amui@gmail.com.
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.
authors.forename: Abdullah Mohammed
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.
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; X-ray Crystallography Unit, School of Physics, Universiti Sains Malaysia, Penang 11800, Malaysia.
authors.forename: Hoong-Kun
authors.initials: HK
authors.lastname: Fun
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: Javed
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
authors.affiliation: Department of Biochemistry, Abdul Wali Khan University, Mardan 23200, Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Wadood
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: C586280:1,4-dihydropyrimidine; D000970:Antineoplastic Agents; D065089:Glycoside Hydrolase Inhibitors; D011743:Pyrimidines; D000520:alpha-Glucosidases
keywords: Cancer cell lines; Cytotoxicity; Molecular docking; Pyrimidines; Spiro heterocycles; α-Glucosidase inhibitors