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TB R&D Weekly Update: Potential Use of Polyether Ionophores Against TB

Kevin DA, Meujo DAF, Hamann MT. Polyether ionophores: broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites. Expert Opinion on Drug Discovery 2009 Feb;4(2):109-146(38). doi:10.1517/17460440802661443.

During this week’s TB R&D Weekly Update, we explore the potential of polyether ionophores as anti-tuberculosis agents in an article published in 2009 by Kevin, et al. Monensin, a known class of antibiotics discovered in 1967, is a polyether ionophore. These compounds are naturally occurring materials generated by a large range of bacteria (e.g. Streptomyces, Actinomadura). They are highly lipophilic with a high molecular weight (500-1000 amu). Their spectrum of activity is quite broad and includes antibacterial, antifungal, antiparasitic, antiviral, antineoplastic activities, anti-inflammatory, immunoregulatory, and CNS activity. Key points to consider regarding polyether ionophores and their use as anti-tuberculosis agents are:

  • These compounds are well-known, naturally occurring, inexpensive, broad spectrum bioactive materials currently used extensively in veterinary medicine against parasites and in food production as a growth promotant.
  • The mechanism of action is through the disruption of ion gradients across cellular membranes.
  • There may be opportunity for synergism with other energy metabolism inhibitors (i.e., TMC207 or clofazimine).
  • There is evidence these compounds exhibit anti-HIV activity (article) and could be used in HIV co-infected TB patients.
  • There is evidence of some cardiovascular and hemodynamic toxicities but these are poorly understood and appear to be species-dependent.

Additional TB R&D News:

Early bactericidal activity of delamanid (OPC-67683) in smear-positive pulmonary tuberculosis patients

Short-course Chemotherapy with TMC-207 and Rifapentine in a Murine Model of Latent Tuberculosis Infection

Incidence of Moxifloxacin Resistance in Clinical Mycobacterium tuberculosis Isolates in Houston, Texas

Next Steps for Tenofovir Gel: Conrad And TIA Sign License Agreement

SCYNEXIS and TB Alliance Sign HEOS Software Agreement

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