title: Structure-activity relationship study of nitrosopyrimidines acting as antifungal agents.
abstract: The design, synthesis, in vitro evaluation, and conformational study of nitrosopyrimidine derivatives acting as antifungal agents are reported. Different compounds structurally related with 4,6-bis(alkyl or arylamino)-5-nitrosopyrimidines were evaluated. Some of these nitrosopyrimidines have displayed a significant antifungal activity against human pathogenic strains. In this paper, we report a new group of nitrosopyrimidines acting as antifungal agents. Among them, compounds 2a, 2b and 15, the latter obtained from a molecular modeling study, exhibited antifungal activity against Candida albicans, Candida tropicalis and Cryptococcus neoformans. We have performed a conformational and electronic analysis on these compounds by using quantum mechanics calculations in conjunction with Molecular Electrostatic Potentials (MEP) obtained from B3LYP/6-31G(d) calculations. Our experimental and theoretical results have led us to identify a topographical template which may provide a guide for the design of new nitrosopyrimidines with antifungal effects.
authors.affiliation: Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 915, 5700 San Luis, Argentina.
authors.forename: Monica
authors.initials: M
authors.lastname: Olivella
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchal
authors.forename: Manuel
authors.initials: M
authors.lastname: Nogueras
authors.forename: Adolfo
authors.initials: A
authors.lastname: Sánchez
authors.forename: Manuel
authors.initials: M
authors.lastname: Melguizo
authors.forename: Marcela
authors.initials: M
authors.lastname: Raimondi
authors.forename: Susana
authors.initials: S
authors.lastname: Zacchino
authors.forename: Fernando
authors.initials: F
authors.lastname: Giannini
authors.forename: Justo
authors.initials: J
authors.lastname: Cobo
authors.forename: Ricardo D
authors.initials: RD
authors.lastname: Enriz
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D041022:Candida tropicalis / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D006860:Hydrogen Bonding; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D009603:Nitroso Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011789:Quantum Theory; D013329:Structure-Activity Relationship
chemical_list: C578263:4-amino-6-phenylamino-2-methoxy-5-nitrosopyrimidine; D000935:Antifungal Agents; D009603:Nitroso Compounds; D011743:Pyrimidines