title: Microwave-assisted synthesis of antimicrobial dihydropyridines and tetrahydropyrimidin-2-ones: novel compounds against aspergillosis.
abstract: Ten 4-aryl-1,4-dihydropyridine and three 4-aryl-1,2,3,4-tetrahydropyrimidin-2-one derivatives have been synthesized and examined for their activity against pathogenic strains of Aspergillus fumigatus and Candida albicans. Although none of the three compounds belonging to pyrimidin-2-one series showed any activity against two pathogens, two of the compounds of the dihydropyridine series, that is, diethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate and dimethyl 4-(4-methoxyphenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate, exhibited significant activity against A. fumigatus in disc diffusion, microbroth dilution and percent spore germination inhibition assays. The most active diethyl dihydropyridine derivative exhibited a MIC value of 2.92 microg/disc in disc diffusion and 15.62 microg/ml in microbroth dilution assays. The MIC(90) value of the most active compound by percent germination inhibition assay was found to be 15.62 microg/ml. The diethyl dicarboxylate derivative of dihydropyridine also exhibited appreciable activity against C. albicans. The in vitro toxicity of the most active diethyl dihydropyridine derivative was evaluated using haemolytic assay, in which the compound was found to be non-toxic to human erythrocytes even at a concentration of 625 microg/ml. The standard drug amphotericin B exhibited 100% lysis of erythrocytes at a concentration almost 16 times less than the safer concentration of the most active dihydropyridine derivative.
authors.affiliation: Institute of Genomics & Integrative Biology, Delhi, India.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chhillar
authors.forename: Pragya
authors.initials: P
authors.lastname: Arya
authors.forename: Chandrani
authors.initials: C
authors.lastname: Mukherjee
authors.forename: Pankaj
authors.initials: P
authors.lastname: Kumar
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Yadav
authors.forename: Ajendra K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Vibha
authors.initials: V
authors.lastname: Yadav
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Gupta
authors.forename: Rajesh
authors.initials: R
authors.lastname: Dabur
authors.forename: Hirday N
authors.initials: HN
authors.lastname: Jha
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Watterson
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Gainda L
authors.initials: GL
authors.lastname: Sharma
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001228:Aspergillosis / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006900:Hydroxylation; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000935:Antifungal Agents; D004095:Dihydropyridines; D011743:Pyrimidines; C030986:pyrimidine