Activity of a new class of isonicotinoylhydrazones used alone and in combination with isoniazid, rifampicin, ethambutol, para-aminosalicylic acid and clofazimine against Mycobacterium tuberculosis

The activities of six derivatives of a new class of isonicotinoylhydrazones were investigated in vitro against Mycobacterium tuberculosis H37Rv ATCC 27294, isoniazid-resistant M. tuberculosis ATCC 35822, rifampicin-resistant ATCC 35838, pyrazinamide-resistant ATCC 35828, streptomycin-resistant ATCC...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2002-02, Vol.49 (2), p.275-282
Main Authors: De Logu, Alessandro, Onnis, Valentina, Saddi, Barbara, Congiu, Cenzo, Schivo, Maria Laura, Cocco, Maria Teresa
Format: Article
Language:English
Subjects:
Aminosalicylic Acid - chemistry
Aminosalicylic Acid - pharmacology
Animals
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - chemistry
Antitubercular Agents - classification
Antitubercular Agents - pharmacology
Biological and medical sciences
Cercopithecus aethiops
Clofazimine - chemistry
Clofazimine - pharmacology
Drug Evaluation, Preclinical - methods
Drug Evaluation, Preclinical - statistics & numerical data
Drug Synergism
Drug Therapy, Combination
Ethambutol - chemistry
Ethambutol - pharmacology
Humans
Hydrazones - chemistry
Hydrazones - pharmacology
Isoniazid - analogs & derivatives
Isoniazid - chemistry
Isoniazid - classification
Isoniazid - pharmacology
Medical sciences
Microbial Sensitivity Tests - statistics & numerical data
Mycobacterium tuberculosis - drug effects
Mycobacterium tuberculosis - isolation & purification
Pharmacology. Drug treatments
Rifampin - chemistry
Rifampin - pharmacology
Vero Cells
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Summary:The activities of six derivatives of a new class of isonicotinoylhydrazones were investigated in vitro against Mycobacterium tuberculosis H37Rv ATCC 27294, isoniazid-resistant M. tuberculosis ATCC 35822, rifampicin-resistant ATCC 35838, pyrazinamide-resistant ATCC 35828, streptomycin-resistant ATCC 35820 and 16 clinical isolates of M. tuberculosis. Several compounds showed interesting antimycobacterial activity against both ATCC strains and clinical isolates, but were less active against isoniazid-resistant M. tuberculosis. Combinations of five isonicotinoylhydrazone derivatives and rifampicin, ethambutol, para-aminosalicylic acid, isoniazid and clofazimine were also investigated against M. tuberculosis H37Rv ATCC 27294 and against ATCC drug-resistant strains. Addition of sub-MICs of some isonicotinoylhydrazone derivatives resulted in a four- to 16-fold reduction in MICs of ethambutol, para-aminosalicylic acid and rifampicin with fractional inhibitory concentrations (FICs) ranging between 0.17 and 0.37, suggesting a synergic interaction against M. tuberculosis H37Rv. Increased activity was also observed with other combinations (FICs 0.53–0.75), including isoniazid, and a synergic interaction between one of the isonicotinoylhydrazone derivatives and isoniazid (FIC 0.26) was shown against isoniazid-resistant M. tuberculosis ATCC 35822, whereas no effects were observed on combining the isonicotinoylhydrazones with clofazimine. The ability of isonicotinoylhydrazones to inhibit specifically the growth of M. tuberculosis, the high selectivity index and their ability to enhance the activity of standard antituberculous drugs in vitro indicate that they may serve as promising lead compounds for future drug development for the treatment of M. tuberculosis infections.
ISSN:0305-7453
1460-2091
1460-2091
DOI:10.1093/jac/49.2.275