Nitroquinolones with broad-spectrum antimycobacterial activity in vitro.
During search on quinolonecarboxylic acids we used a facile, convenient two- or three-step procedure to synthesize new quinolone analogs, bearing at the C-7 position alkylamino substituents, and at the C-6 position a fluorine or alternatively a nitro group. The new derivatives were tested against both Gram-positive and Gram-negative bacteria and against a number of different mycobacteria. In vitro assays showed 1-tert-butyl-7-tert-butylamino-6-nitro-1,4-dihydro-4-quinolone-3-carboxy lic acid to be a potent inhibitor of Streptococcus and Staphylococcus with potencies superior to those of ofloxacin and ciprofloxacin, used as reference drugs. Some 6-nitroquinolones were found to exert good inhibiting activities against Mycobacterium tuberculosis and various atypical mycobacteria, whereas the 6-fluoro counterparts showed poor or no activity against this bacterium.
Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Italy. artico@uniromal.it
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Artico
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Mai
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Sbardella
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Massa
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Musiu
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Lostia
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Demontis
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La Colla
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D008826:Microbial Sensitivity Tests; D009162:Mycobacterium avium / Q000187:drug effects; D020102:Mycobacterium smegmatis / Q000187:drug effects; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D013210:Staphylococcus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
C120932:1-tert-butyl-7-tert-butylamino-6-nitro-1,4-dihydro-4-quinolone-3-carboxylic acid; D042462:4-Quinolones; D000890:Anti-Infective Agents; D015363:Quinolones