Recent Advances in Antituberculous Drug Development and Novel Drug Targets

Haruaki Tomioka, PhD; Yutaka Tatano, PhD; Ko Yasumoto, PhD; Toshiaki Shimizu, PhD

Disclosures

Expert Rev Resp Med. 2008;2(4):455-471. 

In This Article

Abstract and Introduction

Abstract

TB, especially multidrug-resistant TB and extensively drug-resistant TB, is an important global health concern, and the novel development of effective anti-tuberculous drugs is urgently needed. Newly elucidated, critical information on the entire genome of Mycobacterium tuberculosis (MTB) and advances in knowledge regarding various mycobacterial virulence genes are promoting progression in the identification of genes that code for new drug targets. With this background, this review deals with the following areas: first, the future development of new anti-tuberculous drugs is discussed according to the potential pharmacological targets of MTB; and second, a review of the present development status of new anti-tuberculous drugs is conducted, particularly focusing on some promising new anti-tuberculous agents, such as nitroimidazoles, diarylquinolines and oxazolidinones.

Introduction

Worldwide, TB remains the most common and important infectious disease regarding both morbidity and mortality.[1] The WHO estimates that approximately 8.8million new TB cases occur annually worldwide and the incidence of TB is currently increasing; approximately 1.6 million deaths are attributable to TB annually. Thus, TB is a major global health concern. In addition, multidrug-resistant TB (MDR-TB) and, especially, extensively drug-resistant TB (XDR-TB), are currently increasing in incidence in many areas around the world. However, the development of new drugs for the treatment and prophylaxis of TB has been slow. No new drugs, except for pyrazinamide (PZA), rifabutin and rifapentine, have been approved for TB treatment over the 40years since the release of rifampin (RIF). Although several drugs, such as nitroimidazole compounds, diarylquinoline and oxazolidinones, are currently under development, it is a matter of urgency to develop other new anti-tuberculous drugs, especially with the aid of bioinformatics-based drug design, in order to tackle intractable TB.[1,2,3,4,5,6,7] It is important to develop drugs useful for the chemical prophylaxis of TB in persons with latent Mycobacterium tuberculosis (MTB) infection and the clinical control of MDR-TB and XDR-TB. The present status of the development of promising new antimicrobials with anti-MTB activity, particularly regarding new drug targets of MTB, will be discussed.

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