title: Synthesis of N-aryl and N-arylcarbamoylamino derivatives of 1,3-diazinane-5-carboxamide and their activity against glioblastoma LN-229 cell line.
abstract: Six structural motifs based on the initial (lead) structure of merbarone were designed, prepared, and tested against the glioblastoma LN-229 cell line. Three different structural moieties were modified in the search for optimal glioblastoma activity: the 1,3-diazinane moiety, the aryl moiety, and the heteroatom linker. Calculated molecular descriptors such as lipophilicity (ClogP), acidic strength (calculated pKa), and polar surface area (PSA) were used to design a diverse structural library of these compounds. From six different structural motifs and 136 compounds, a handful of examples with moderate (100μg/ml), good (10μg/ml) and excellent (1μg/ml) glioblastoma activity were elucidated.
authors.affiliation: Department of Chemistry, University of New Orleans, New Orleans, LA 70148, United States.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Hron
authors.affiliation: Department of Chemistry, University of New Orleans, New Orleans, LA 70148, United States; STEPHARM, LLC., PO Box 24220, New Orleans, LA 70184, United States.
authors.forename: Branko S
authors.initials: BS
authors.lastname: Jursic
authors.affiliation: Louisiana State University Health Sciences Center, Department of Pharmacology and Experimental Therapeutics, 1901 Perdido St., New Orleans, LA 70112, United States; Department of Ophthalmology, LSUHSC, New Orleans, United States.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Neumann
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001463:Barbiturates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002219:Carbamates / Q000737:chemistry; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma; D006801:Humans; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013858:Thiobarbiturates / Q000737:chemistry; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001463:Barbiturates; D002219:Carbamates; D010671:Phenylurea Compounds; D013858:Thiobarbiturates; D059005:Topoisomerase II Inhibitors; C045459:merbarone
keywords: Anticancer; Carbamoyl; Diazinane; Glioblastoma; Merbarone