Antimycobacterials

During the most active period of investigation of sulfanilamide derivatives, 1935—1944, for systemic bacterial infections, the antimycobacterial activity of 4,4 -dianainodiphenylsulfone [80-08-8] (DDS, dapsone) was discovered (14). Although neither this compound nor its derivatives proved to be clinically usehil for human tuberculosis, it did evolve into the most important type of compound for leprosy (15). The diacetyl derivative has also... 

Gapreomycin, Viomycin, and Enviomycin. Capreomycin (Capastat, Lilly), a bacteriostatic, antimycobacterial peptide mixture isolated from Streptomjces capreolus was first reported in 1961 (106—108). This tuberactinomycin family member, shown in Table 4, was introduced into the U.S. market in 1971 where it has remained a usehil but nephrotoxic and ototoxic second-line alternative to first-line tuberculosis therapies. Because capreomycin is somewhat less toxic than viomycin (tuberoactinomycin B [32988-50-4]) C25H42N23O2Q (109,110), capreomycin has now displaced viomycin in the United States and most other markets. The stmcture of viomycin is shown in Figure 2. The related enviomycin (tuberactinomycin N [33103-22-9]), C23H43N23O2Q,... 

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. 

Borgaonkar MR, Macintosh DG, Fardy JM A meta-analysis of antimycobacterial therapy for Crohn s disease. Am J Gastroenterol 2000 95 725-729. 

Pereira CG, Leal PF, Sato DN and Meireles MAA. 2005. Antioxidant and antimycobacterial activities of Tabernaemontana catharinensis extracts obtained by Supercritical CO2 +cosolvent. J Med Food 8(4) 533—538. 

The answer is b. (Hardmanr p 1158.) Isoniazid inhibits cell-wall synthesis in mycobacteria. Increasing vitamin B6 levels prevents complications associated with this inhibition, including peripheral neuritis, insomnia, restlessness, muscle twitching, urinary retention, convulsions, and psychosis, without affecting the antimycobacterial activity of INH. 

Antimycobacterials Isoniazide 10-15 mg/kg once daily 5 mg/kg once daily... 

Bosi S, Da Ros T, Castellano S, Banfi E, Prato M (2000) Antimycobacterial activity of ionic fullerene derivatives. Bioorg. Med. Chem. Lett. 10 1043-1045. 

More recent investigations on the antimycobacterial activity of pamamycin-607 (lb) on 25 independent M. tuberculosis clinical isolates (either susceptible, mono-, or multiresistant to the first line antituberculous drugs) established minimum inhibitory concentrations MICjoo in the range of 1.5-2.0 pg/ml, while the MICjoo of lb for a bioluminescent laboratory strain of M. tuberculosis (H37Rv) was determined as 0.55 pg/ml [3a]. Parallel studies on the effect of lb on the cell cycle distribution of human (HL-60) cells by flow cytometry indicated no... 

Barry CE, Slayden RA, Sampson AE, Lee RE. (2000) Use of genomics and combinatorial chemistry in the development of new antimycobacterial dmgs. Biochem Pharmacol 59 221-231. 

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. 

Rojas R, Bustamante B, Ventosilla P, Femmidez I, Caviedes L, Gilman RM, Lock O, Hammond GB. (2006) Larvicidal and antimycobacterial and antifungal compounds from the bark of the Peruvian plant Swartzia polyphylla DC. Chem Pharm Bull 54 278-279. 

Boonphong S, Puangsombat P, Baramee A, Machidol C, Ruchirawat S, Kittakoop P. (2007) Bioactive compounds from Bauhinia purpurea possessing antimalarial, antimycobacterial, antifungal, anti-inflammatory and cytotoxic activities. J Nat Prod 70 795-801. 

Leon-Rivera I, Miron-Lopez G, Molina-Salinas GM, Herrera-Ruiz M, Estrada-Soto S, Gutierrez M, Alonso-Cortes D, Navarrete-Vasquez G, Rios M, Said-Femandez S (2008) Tyrianthinic Acids from Ipomoea tyrianthina and Their Antimycobacterial Activity, Cytotoxicity and Effects on the Central Nervous System. J Nat Prod 71 1686... 

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... 

Table 1. Bioactive fungal products from endophytic fungi in recent literature reviews. The compounds include antifungal, antibacterial, antimycobacterial, antiviral, nematicidal, cytotoxic, antineoplastic, antioxidant, antiinsectant, antifeedant, antidiabetic, herbicidal, algicidal, specific en mie inhibitory, and immunomodulatory activities. 

Mycobacterial infections - Recommended as the primary agent for the treatment of disseminated MAC. Use in combination with other antimycobacterial drugs that have shown in vitro activity against MAC. 

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... 

Children Safety and efficacy in children have not been established. Limited safety data are available from treatment use in 22 HIV-positive children with MAC who received rifabutin in combination with at least 2 other antimycobacterials for periods from 1 to 183 weeks. Mean doses (mg/kg) for these children were 18.5 for infants 1 year of age 8.6 for children 2 to 10 years of age and 4 for adolescents 14 to 16 years of age. There is no evidence that doses greater than 5 mg/kg/day are useful. Precautions... 

---