Synthesis, anti-mycobacterial, anti-trichomonas and anti-candida in vitro activities of 2-substituted-6,7-difluoro-3-methylquinoxaline 1,4-dioxides.
A new series of 23 6,7-difluoro-3-methyl-2-phenylthio/phenylsulfonyl/phenylsulfinyl/benzylamino/phenylamino-quinoxaline 1,4-dioxides variously substituted in the phenyl moiety, was synthesized and submitted to in vitro evaluation for anti-mycobacterial, anti-trichomonas, anti-candida, anti-mycoplasma and antibacterial activities. In anti-mycobacterial assays, several compounds resulted active (MIC90 = 2.0-4.0 microg/ml) against Mycobacterium tuberculosis H37Rv. Anti-trichomonas screening showed a generally good activity of all compounds (MBC = 0.39-25.0 microg/ml) versus Trichomonas vaginalis, in particular the derivatives 5a,d, 7a, 9 and 11c ranged 0.39-0.78 microg/ml (metronidazole MBC = 12.5 microg/ml). Results of anti-candida assays showed that derivatives 7a, 8a,d and 9 were active against several species of Candida (C. albicans, C. krusei, C. parapsilosis and C. glabrata), having MIC50 between 3.9 and 31.25 microg/ml. The latter compounds were also submitted to anti-mycoplasma assay against Mycoplasma hominis, the results obtained showed that 7a, 8a,d and 9 inhibited the growth of the mycoplasma at the concentration of 0.1 mg/ml. In antibacterial tests only a few compounds showed an MIC50 lower than 62.5 microg/ml against representative strains of Gram-positive and Gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Vibrio alginolyticus and Pseudomonas aeruginosa).
Dipartimento Farmaco Chimico Tossicologico, via Muroni 23/a, 07100 Sassari, Italy. acarta@ssmain.uniss.it
Antonio
A
Carta
Mario
M
Loriga
Giuseppe
G
Paglietti
Antonella
A
Mattana
Pier Luigi
PL
Fiori
Paola
P
Mollicotti
Leonardo
L
Sechi
Stefania
S
Zanetti
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000994:Antitrichomonal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014246:Trichomonas vaginalis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000994:Antitrichomonal Agents; D011810:Quinoxalines