Isonicotinoylhydrazone analogs of isoniazid: relationship between superoxide scavenging and tuberculostatic activities.
Superoxide scavenging activity (SSA) of recently synthesized isonicotinoylhydrazones, analogs of the clinically used anti-tuberculosis drug isoniazid (INH), was investigated using xanthine/xanthine oxidase system to generate the superoxide anion. The isonicotinoylhydrazones exhibited well expressed SSA, whereas INH did not show any SSA. All of the isonicotinoylhydrazones had a tuberculostatic activity when tested with the standard strain of Mycobacterium tuberculosis H(37)R(v) and some of them had a higher tuberculostatic activity than INH. A lower acute toxicity was also observed compared to INH. Moreover, a correlation was observed between LD(50) and SSA for the isonicotinoylhydrazones studied. An explanation is suggested for the higher tuberculostatic activity and lower acute toxicity of some of the isonicotinoylhydrazones as compared to that of INH. A new route to less toxic derivatives of INH with potential tuberculostatic activity is proposed.
Georgieva
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Department of Physiology and Chemistry, Faculty of Veterinary Medicine, Thracian University, 6000 Stara Zagora, Bulgaria..
Gadjeva
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D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism*; D023382:Toxicity Tests, Acute
D000995:Antitubercular Agents; D016166:Free Radical Scavengers; D013481:Superoxides; D007538:Isoniazid