title: Novel synthesis of dihydropyrimidines for α-glucosidase inhibition to treat type 2 diabetes: in vitro biological evaluation and in silico docking.
abstract: A convenient and efficient new method has been established for the synthesis of dihydropyrimidines by inexpensive and non-toxic N-acetyl glycine (NAG) catalysed reaction of aromatic aldehydes with ethyl acetoacetate and urea/thiourea. This method is applicable for various substituted aldehydes as well as urea and thiourea. It has also been used to synthesize bicyclic oxygen-bridged pyrimidine derivatives (4d, 4j). The biological assay revealed that the majority of compounds synthesized displayed modest inhibitory activity against α-glucosidase at low micro-molar concentrations. Molecular docking studies were also performed on the most active compound, 4f (with IC50 value 112.21±0.97 μM), to show the enzyme - inhibitor interactions.
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan. Electronic address: drmyar@ciitlahore.edu.pk.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Yar
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland; Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688 Cracow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bajda
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
authors.forename: Lubna
authors.initials: L
authors.lastname: Shahzadi
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan. Electronic address: sohail_chem@yahoo.com.
authors.forename: Sohail Anjum
authors.initials: SA
authors.lastname: Shahzad
authors.affiliation: Department of Chemistry, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Maqsood
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Biochemistry & Biotechnology, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan.
authors.forename: Umber
authors.initials: U
authors.lastname: Alam
authors.affiliation: Department of Chemistry, GC University, Lahore 54000, Pakistan.
authors.forename: Islam Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Interdisciplinary Research Center in Biomedical Materials, COMSATS Institute of Information Technology, Lahore 54000, Pakistan.
authors.forename: Ather Farooq
authors.initials: AF
authors.lastname: Khan
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D065089:Glycoside Hydrolase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism*
chemical_list: C586280:1,4-dihydropyrimidine; D065089:Glycoside Hydrolase Inhibitors; D011743:Pyrimidines; D000520:alpha-Glucosidases
keywords: Acarbose; Biginelli reaction; Dihydropyrimidine; N-acetyl glycine; α-Glucosidase inhibitors