New series of isoniazid hydrazones linked with electron-withdrawing substituents.
A series of new isoniazid hydrazones was synthesized by two procedures. In the first isoniazid was activated with diethoxymethyl acetate and condensed with the appropriate anilines. Alternatively, substituted anilines were activated by diethoxymethyl acetate and subsequently condensed with isoniazid. NMR study confirmed that both synthetic approaches gave the same tautomer. All compounds were screened for in vitro antimycobacterial activity. Most of them exhibited the same activity against Mycobacterium tuberculosis (MIC 1 μmol L(-1)) as isoniazid (INH), better activity against Mycobacterium kansasii 325/80 (MIC 0.125-0.250 μmol L(-1)), high value of selectivity index (SI) and IC(50) between 0.0218 and 0.326 mmol L(-1). Compound 2o with the best SI was used as a model compound for the stability test and was found to be stable at neutral pH, but under acidic conditions it slowly hydrolysed.
Charles University, Faculty of Pharmacy, Department of Inorganic and Organic Chemistry, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic. evavavrikova@seznam.cz
Eva
E
Vavříková
Slovenko
S
Polanc
Marijan
M
Kočevar
Janez
J
Košmrlj
Kata
K
Horváti
Szilvia
S
Bosze
Jiřina
J
Stolaříková
Aleš
A
Imramovský
Jarmila
J
Vinšová
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D007538:Isoniazid / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy; D015269:Mycobacterium avium Complex / Q000187:drug effects; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy; D019909:Mycobacterium kansasii / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D014376:Tuberculosis / Q000188:drug therapy
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D006835:Hydrazones; D007538:Isoniazid