title: Synthesis and biological evaluation of novel oxadiazole derivatives: a new class of thymidine phosphorylase inhibitors as potential anti-tumor agents.
abstract: Based on the fact that the thymidine phosphorylase inhibitors are considered potential anti-tumor agents, a range of novel oxadiazole derivatives 3a-3u was designed and synthesized by a simple and facile synthetic route. The biological assay revealed that majority of compounds displayed modest inhibitory activity against thymidine phosphorylase at low micromolar concentrations (IC50 173.23±3.04 to 14.40±2.45μM). In the current study the most active compounds were 3h and 3q with IC50 values 14.40±2.45 and 17.60±1.07μM, respectively. Molecular docking studies were performed on the most active compounds (3h, 3k, 3o-3q) to show their binding mode.
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: 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: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Bushra
authors.initials: B
authors.lastname: Jadoon
authors.affiliation: Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
authors.forename: Zulfiqar Ali
authors.initials: ZA
authors.lastname: Khan
authors.affiliation: Department of Chemistry, Government College University, Faisalabad 38000, Pakistan.
authors.forename: Syed Ali Raza
authors.initials: SA
authors.lastname: Naqvi
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Ahson Jabbar
authors.initials: AJ
authors.lastname: Shaikh
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Khizar
authors.initials: K
authors.lastname: Hayat
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
authors.forename: Adeem
authors.initials: A
authors.lastname: Mahmmod
authors.affiliation: Department of Allied Sciences and Chemical Pathology, University of Health Sciences, Lahore 54600, Pakistan.
authors.forename: Nasir
authors.initials: N
authors.lastname: Mahmood
authors.affiliation: Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Filipek
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D013939:Thymidine Phosphorylase
keywords: 1,3,4-Oxadiazole-2-thione; Angiogenesis; Anti-cancer activity; Mannich bases; Thymidine phosphorylase inhibitors