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Eur J Pharm Sci ; 137: 104974, 2019 Sep 01.
Article in English | MEDLINE | ID: mdl-31252051

ABSTRACT

Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs. Prevention of adverse reactions, increase treatment adherence and success rates, providing better control of tuberculosis (TB). In this regard, obtaining new drugs with low toxicity and high tuberculostatic potential is essential. Thus, in this work, we have designed or synthesized new derivatives of isoniazid (INH), such as new Isonicotinoylhydrazone (INH-a, INH-b and INH-c). These derivatives demonstrated good biocompatibility, antimicrobial property similar to that of parent isoniazid and last but not least, a significantly improved Pharmacotoxicological profile compared to that of isoniazid.


Subject(s)
Antitubercular Agents , Hydrazones , Isoniazid/analogs & derivatives , Animals , Antitubercular Agents/pharmacology , Antitubercular Agents/toxicity , Cell Line , Cell Survival/drug effects , Hydrazones/pharmacology , Hydrazones/toxicity , Isoniazid/pharmacology , Isoniazid/toxicity , Lethal Dose 50 , Male , Mice , Mycobacterium tuberculosis/drug effects , Toxicity Tests, Acute , Toxicity Tests, Chronic
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