Isonicotinoylhydrazone Analogs of Isoniazid: Relationship between Superoxide Scavenging and Tuberculostatic Activities

N. Georgieva¹ and V. Gadjeva^2*

¹Department of Physiology and Chemistry, Faculty of Veterinary Medicine, Thracian University, 6000 Stara Zagora, Bulgaria; fax: +359-42-600-005

²Department of Chemistry and Biochemistry, Medical Faculty, 11 Armeiska st., Thracian University, 6000 Stara Zagora, Bulgaria; fax: +359-42-600-005; E-mail: vgadjeva@mf.uni-sz.bg

^* To whom correspondence should be addressed.

Received August 15, 2001; Revision received September 22, 2001

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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 H₃₇R_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 LD₅₀ 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.

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KEY WORDS: isonicotinoylhydrazones, superoxide scavenging activity, anti-tuberculosis, isoniazid

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