Mycobacterium tuberculosis analogues

S. C. Almo, and V. L. Schramm, Over-the barrier transition state analogues and crystal stmcture with Mycobacterium tuberculosis purine nucleoside phosphorylase, Biochemistry, 42 (2003) 6057-6066. 

Anand R, Somasundaram S, Doble M, Paramasivan C (2011) Docking studies on novel analogues of 8 methoxy fluoroquinolones against GyrA mutants of Mycobacterium tuberculosis. BMC Struct Biol 11 47... 

Renilla (sea pansy) luciferin (and certain of its synthetic analogues) produces a brilliant blue chemiluminescence when dissolved in organic solvents such as dimethylformamide and involves the anion of 2-acetamido-3-benzyl-5-(p-hydroxy-phenyl)pyrazine (21) (1191). 5-Hydrazino-2-hydrazinocarbonylpyrazine is effective against mycobacterium tuberculosis and m. kansasii in vitro (1098). Aminonitro-pyrazines have been claimed as useful yellow dyes for wool (1180) and tetraamino-pyrazine (1180) and A -substituted amides of 2-carboxy-3,5-bismethylamino-6-(A -methylcarbamoyl)pyrazines (1192) as fluorescent brighteners (or optical bleaching agents) for textiles. 

Pjrazinamide is a pyrazine analogue of nicotinamide. It is bactericidal for Mycobacterium tuberculosis in an acid environment and within macrophages (1). Regimens that include pyrazinamide produce significantly more rapid rates of sputum conversion than any other combination. Pyrazinamide is therefore especially appropriate in the initial phase of treatment. In the 6-month... 

Bonnac, L., Gao, G.Y., Chen, L., et al. (2007) Synthesis of 4-phenoxybenzamide adenine dinucleotide as NAD analogue with inhibitory activity against enoyl-ACP reductase (InhA) of Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett. 17, 4588 591. 

Diverse thio analogues of purine have been prepared as anti-Mycobacterium tuberculosis agents. Two of them, 9-(ethylcarboxymethyl)-6-(decylthio)-9//-purine and 9-(ethylcarboxymethyl)-6-(dodecylthio)-9f/-purine proved to be particularly active <04JMC273>. 

Precursor-directed biosynthesis has produced novel analogues of the massetolides (2-9), cyclic depsipeptides [9]. This is a promising family of natural products as massetolide A (2) exhibits potent, selective activity against Mycobacterium tuberculosis, the causative agent for tuberculosis, and Mycobacterium avium-intracellulare, a bacterium which causes... 

The synthesis of analogues of isonicotinamide resulted in the discovery of ethionamide and a homologue in which the ethyl group is replaced with a propyl (prothionamide). Both compounds have proven to be bactericidal against Mycobacterium tuberculosis and Mycobacterium leprae. 

Novel inhibitors of Mycobacterium tuberculosis growth based on modified pyrimidine nucleosides and their analogues 13UK896. 

Tuberculosis still remains a major health problem in the world, with almost 1.5 million deaths annually. Sulfoglycolipids were identified as new mycobacterium antigens able to control mycobacterial infection" and appeared to be promising additive candidates for the development of a new tuberculosis vaccine. These complex metabolites are acylated and sulfated a,a-D-trehalose derivatives which are found in the cell wall of Mycobacterium tuberculosis (Scheme 16)." Efficient access to di-O- and tetra-O-acylated sulfoglycolipid analogues have been developed by using the iron(iii) chloride-catalyzed tandem protocol for the functionalization of C2 symmetric a,a-D-trehalose. ... 

The hydrolytic stability of branched RNA where the branch-point is a phospho-triester unit revealed that when the triester was embedded within the oligonucleotide it was stable to base-mediated hydrolysis by more than an order of magnitude compared to the simple trinucleotide unit. 5 -Aminoalkyl phosphate nucleotides have been synthesised as analogues of aminoacyl adenylates, and salicyl phospho-diesters of adenylates as potential inhibitors of Mycobacterium tuberculosis. ... 

Cinnamaldehyde derivatives (457) were synthesised in good to excellent yields in one step by a mild and selective, base free, palladium(II)-catalysed, oxidative Heck reaction starting from acrolein methyl vinyl ketone (455) and various arylboronic acids (456) (Scheme 113). The aldehydes (457) were used for synthesis of novel a-aryl substituted fosmidomycin analogues (458), which were evaluated for their inhibition of Mycobacterium tuberculosis l-deoxy-Z)-xylulose 5-phosphate reductoisomerase. The best compound showed activity comparable to that of the most potent, previously reported a-aryl substituted fosmidomycin class inhibitor. 

Karlen et al. have synthesised aryl substituted fosmidomycin analogues (823) which had more favorable physicochemical properties and were also more active in inhibiting malaria parasite growth. Biological evaluation showed that it was potent on MtDXR Mycobacterium tuberculosis DXR) (R = Cl, Cl R = R = H, IC50 = 0.15 pM) but that it still lacked activity on M. tuberculosis whole cells (MIC>32pg/mL). ... 

Nucleoside and nucleotide analogues have been widely used in the treatment of various diseases. Koegler et al. reported the synthesis of 6-aza-2 -deo3qruridine monophosphate analogues (6). These compounds can inhibit thymidylate synthases, and also act as substrates or inhibitors of thymidine monophosphate kinase in mycobacterium tuberculosis. 

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