Antimycobacterial agents

The cell walls of mycobacteria contain three structures peptidoglycan, an arabinogalactan polysaccharide and long chain hydroxy fatty acids (mycolic acids) which are all covalently linked. Additional non-covalently attached lipid components found in the wall include glycolipids, various phospholipids and waxes. The lipid-rich nature of the mycobacterial wall is responsible for the characteristic acid-fastness on staining and serves as a penetration barrier to many antibiotics. Isoniazid and ethambutol have long been known as specific antimycobacterial agents but their mechanisms of action have only recently become more clearly understood. 

Rivero-Crnz I, Acevedo L, Guerrero JA, Martinez S, Pereda-Miranda R, Mata R, Bye R, Franzblau S, Timmermann BN. (2010) Antimycobacterial agents from selected Mexican medicinal plants. J Pharm Pharmacol 57 1117-1126. 

Patole J, Shingnapurkar D, Padhye S, Ratledge C, Schiff base conjugates of /)-aminosalicylic acid as antimycobacterial agents, Bioorg Med Chem Lett 16 ... 

Chomcheon P, Wiyakrutta S, Sriubolmas N, Ngamrojanavanich N, Isarangkul D, Kittakoop P 3-Nitropropionic acid (3-NPA), a potent antimycobacterial agent... 

Pharmacology Rifabutin, an antimycobacterial agent, is a semisynthetic ansamycin antibiotic derived from rifamycin S. It is not known whether rifabutin inhibits DNA-dependent RNA polymerase in Mycobacterium avium or in Mycobacterium... 

Resistance M. tubercuiosis organisms resistant to other rifamycins are likely to be resistant to rifapentine. Cross-resistance does not appear between rifapentine and non-rifamycin antimycobacterial agents such as isoniazid and streptomycin. 

Drug X is an antimycobacterial agent that inhibits other bacteria as well as poxviruses. However, It should not be used as a single agent because resistant mutants frequently form. The responsible mutation may alter the site of action of drug X [l.e., the deoxyribonucleic acid (DNA)-dependent ribonucleic acid (RNA) polymerase]. What Is drug X ... 

Naturally occurring benzoxazoles of marine origin are rare, but two new structurally related compounds of this type have been isolated. One of these, pseudopteioxazole 58, is a [>otent antimycobacterial agent <990L527>. ... 

In the framework of a synthesis of antimycobacterial agents, acid chloride 134 was reacted with 2-aminophenol 115 and base. The isolated product 135 underwent a base-mediated ring closure to form tricyclic benzoxazepines 136 (Scheme 18) <2000AP231>. The same procedure has been used for the synthesis of multidrug resistance modulating agents <2004JME4627>. 

Biava M, Porretta GC, Poce G et al (2006) Antimycobacterial agents. Novel diarylpyrrole derivatives of BM212 endowed with high activity toward Mycobacterium tuberculosis and low cytotoxicity. J Med Chem 49 4946 952... 

Kumar RR, Perumal S, Senthilkumar P et al (2008) A highly atom economic, chemo-, regio-and stereoselective synthesis, and discovery of spiro-pyrido-pyrrolizines and pyrrolidines as antimycobacterial agents. Tetrahedron 64 2962-2971... 

Selective reduction of m-dinitrobenzene (121) followed by, successively, diazotiza-tion, introduction of hydroxyl, reduction of the nitro group and carboxylation, yields the antimycobacterial agent p-aminosalicylic acid (122) (Scheme 25) used with the antibiotic streptomycin. A three-step synthesis starting with toluene yields the inexpensive drug thioacetazone (123). 

I Ethionamide. Ethionamide shares structural features with two other antimycobacterial agents, isoniazid and, more distantly, thiac-etazone, a drug not used in the United States. Prothionamide, the n-propyl derivative of ethionamide, is used in Europe. Ethionamide is only active against organisms of the genus Mycobacterium, and it should be considered primarily bacteriostatic because it is difficult to achieve serum concentrations that would be bactericidal. " " ... 

Beming SE, Peloquin CA. Antimycobacterial agents Isoniazid. In Yu VL, Merigan TC, Barriere S, White NJ, eds. Antimicrobial Chemotherapy and Vaccines. Baltimore, Williams Wilkins, 1998 654-4)63. 

Treatment regimens for Mycobacterium avium complex infection should contain at least two antimycobacterial agents. Every regimen should contain either clarithromycin or azithromycin plus a second agent such as ethambutol. 

Arain TM, Resconi AE, Sing DC, Stover CK. Reporter gene technology to assess activity of antimycobacterial agents in macrophages. Antimicrobial Agents Chemother 1996 40 1542-4. 

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