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1 2016

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Płoszaj P., Piwowar A., Ryng S.

Wiadomości Chemiczne

2016

[Z] 70, 1-2

35--56

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) remains a leading cause of morbidity and mortality in developing countries [1]. With the discovery of chemotherapeutic agents in the 1940s and implementation of directly- -observed therapy short course (DOTS) in the 1980s, it was believed that TB would decline globally. Although a declining trend was observed in most developed countries, this was not evident in other parts of the world [2]. In addition, the rate of successful treatment has been compromised in recent years due to the increasing prevalence of multidrug-resistant (MDR-) and extensively drug-resistant TB ( XDR-TB) strains [3]. Accordingly, significant efforts have been made to discover and develop new treatment modalities against TB. This article serves as a summary of the most recent developments in search for novel anti-tubercular compounds. Here we focus on reviewing the results of basic research and clinical trials obtained in 2015 including: a) the phase IV clinical trials conducted for newly developed: bedaquiline, delamanid, clofazimine (previously registered for treatment of leprosis) b) phase III for fixed-dose combination of existing drugs: pretomanid – moxifloxacin – pyrazinamide) and c) the phase II clinical trials for sutezolid, AZD5847 and SQ109 [4]. All newly developed compounds used in these studies have been briefly characterized and their synthesis pathways fully described. In addition we review the most recent and promising results on nicotinic acid hydrazides, thienyl-pirimidines imidazole- -thiadiazole-benzimidazole and benzocoumarine derivatives presenting their synthesis pathways, most active chemical structures and their potential applications. Throughout this paper the ultimate direction for new drug development strategies, in search for the anti-tubercular agents, have been reviewed.