title: Sulfur and selenium derivatives of quinazoline and pyrido[2,3-d]pyrimidine: synthesis and study of their potential cytotoxic activity in vitro.
abstract: The synthesis, cytotoxic activities and selectivities of 35 derivatives related to quinazoline and pyrido[2,3-d]pyrimidine are described. The synthesized compounds were screened in vitro against four tumoral cell lines - leukemia (CCRF-CEM), colon (HT-29), lung (HTB-54) and breast (MCF-7) - and two cell lines derived from non-malignant cell lines, one mammary (184B5) and one from bronchial epithelium (BEAS-2B). MCF-7 and HTB-54 were the most sensitive cell lines with GI(50) values below 10μM for eleven and ten compounds, respectively. Two compounds (2o and 3a) were identified that evoked a marked cytotoxic effect in all cell lines tested and one compound, 7h, was potent and selective against MCF-7. A preliminary study into the mechanism of the potent derivatives 2o, 3a and 7h indicated that the cytotoxic activities of these compounds might be mediated by inducing cell death without affecting cell cycle phases.
authors: Sección de síntesis, Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea, 1, E-31008 Pamplona, Spain.
authors: Esther
authors: E
authors: Moreno
authors: Daniel
authors: D
authors: Plano
authors: Iranzu
authors: I
authors: Lamberto
authors: María
authors: M
authors: Font
authors: Ignacio
authors: I
authors: Encío
authors: Juan Antonio
authors: JA
authors: Palop
authors: Carmen
authors: C
authors: Sanmartín
mesh_terms: D000042:Absorption; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D012643:Selenium / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D011799:Quinazolines; D013455:Sulfur; D012643:Selenium; C030986:pyrimidine