Current Topics in Medicinal Chemistry - Volume 12, Issue 7, 2012

Tuberculosis (TB) remains the second leading cause of infectious disease mortality superseded only by HIV. The etiological agent of TB is Mycobacterium tuberculosis (Mtb), a slow-growing bacillus, which can switch its metabolism to a latent nonreplicating state. The recommended therapy for treatment of TB involves four drugs taken for at least 6 months, referred to as “first-line” drugs due to their high efficacy an Read More

The bacterial type II fatty acid biosynthesis (FASII) pathway is an essential but unexploited target for drug discovery. In this review we summarize SAR studies on inhibitors of InhA, the enoyl-ACP reductase from the FASII pathway in M. tuberculosis. Inhibitor scaffolds that are described include the diaryl ethers, pyrrolidine carboxamides, piperazine indoleformamides, pyrazoles, arylamides, fatty acids and imidazopiperidines, all Read More

Antiviral chemotherapy often relies on nucleoside analogues, which, once phophorylated by intracellular kinases, target viral polymerases impeding DNA synthesis. In contrast, nucleoside analogues are much less explored as antibacterial drugs. Thymidine monophosphate kinase from Mycobacterium tuberculosis (TMPKmt), which is essential to DNA replication, was selected as a promising target for the design of new in Read More

Isoprene biosynthesis is an essential component of metabolism. Two pathways are known for the production of five-carbon (isoprene) intermediates: the mevalonate and nonmevalonate pathways. As many pathogenic organisms rely exclusively on the nonmevalonate pathway (NMP) for isoprenoids and humans do not, the enzymes of this route have been recently explored as new therapeutic targets. The secon Read More

New antituberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis (Mtb) strains and to shorten the long treatment regimen. A series of isoxazole-based compounds, bearing a carboxy moiety at the C3 position, are highly potent and versatile anti-TB agents. Several members of this compound class exhibit submicromolar in vitro activity against replicating Mtb (R-TB) and thus compara Read More

New therapeutics are urgently needed to combat the immense disease burden of tuberculosis and related mycobacterial diseases worldwide. Natural products continue to provide leads for the development of novel drugs to treat the rapidly growing numbers of patients with multi- and extensively-drug resistant tuberculosis. This review presents natural products and synthesized analogues with anti-mycobacterial activity Read More

Adenylation or adenylate-forming enzymes (AEs) are widely found in nature and are responsible for the activation of carboxylic acids to intermediate acyladenylates, which are mixed anhydrides of AMP. In a second reaction, AEs catalyze the transfer of the acyl group of the acyladenylate onto a nucleophilic amino, alcohol, or thiol group of an acceptor molecule leading to amide, ester, and thioester products, Read More

Manuel A. de Pablo Martinez was born in Jaén (Spain) in 1967. He obtained his first University degree in 1991 at the University of Granada (Spain), and his Ph.D. in Biology at the University of Jaen in 1995 where he received a special doctorate award with his thesis, “The effect of an olive oil rich diet on the immune system”. His work became the origin of new research at the University of Jaen. Dr. de Pablo was assistant Professor Read More