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This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Several quinonoid and phenazine compounds were synthesized in moderate to high yields and showed activity against H(37)Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The cytotoxity of the compounds were evaluated against human peripheral blood mononuclear cells (PBMC) and these substances emerge as promising antitubercular prototypes., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Tuberculosis is still a major health problem worldwide. Although treatment regimens currently available can cure almost all tuberculosis drug susceptible cases, problems such as the length of treatment, the need for multidrug therapy, the emergence of drug resistance, HIV co-infection and persistent Mycobacterium tuberculosis bacilli, stress the need for new anti-tuberculosis drugs. Strategies to search for new anti-tuberculosis drugs involve: screening libraries of small molecules and natural products or the previous identification of targets crucial to the microorganism and the subsequent design of new molecules. Development of new drugs from known compounds having already shown safety and efficacy is an attractive strategy from the economical, pharmaceutical and clinical point of view. Several derivatives of known molecules and new compounds with different targets have been studied with promising preliminary results. Anti-tuberculosis compounds from natural sources have an enormous potential for the development of new drugs, which have shown not only antimicrobial activity per se but also inhibition of the mechanism of resistance (e.g. efflux pumps) or modulation of the immune response (e.g. macrophage stimulation). If these new drugs are going to have an impact in the treatment of the disease they should ideally be active not only against multiplying microorganisms but also against persistent or dormant bacilli. Due to the complexity of the pathology of M. tuberculosis it is unlikely that a single new drug will be enough. This review will discuss strategies for evaluating drug candidates, new targets, new compounds obtained from synthesis and natural sources, and clinical trials that are currently in progress.

Rapid, accurate and inexpensive methods are essential to detect drug-resistant Mycobacterium tuberculosis and allow timely application of effective treatment and precautions to prevent transmission. The proportion method, the MTT and Alamar Blue redox methods, and the D29 mycobacteriophage assay, were compared for their ability to detect resistance to isoniazid and rifampicin. When tested against a panel of known M. tuberculosis strains, the redox methods and the D29 assay showed good sensitivity and specificity compared to the proportion method, suggesting that they could be useful alternatives for identifying multidrug resistance in M. tuberculosis.