Rifamycin derivatives active against pathogenic rapidly-growing mycobacteria

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2112-2115. doi: 10.1016/j.bmcl.2019.07.001. Epub 2019 Jul 2.

Abstract

Infections due to rapidly growing mycobacteria (RGM), and in particular the RGM species Mycobacterium abscessus (Mab), are very difficult to treat and reports on novel therapeutic options are scarce. A hallmark of all pathogenic RGM species is their resistance to the four first-line drugs used to treat infections with Mycobacterium tuberculosis including rifampicin. This study demonstrates that modification of the rifampicin scaffold can restore rifampicin activity against the three most commonly isolated pathogenic RGM species including Mab. We also note that the structure-activity relationship for Mab is different as compared to the non-pathogenic RGM species Mycobacterium smegmatis.

Keywords: Abscessus; Chelonae; Fortuitum; Mycobacterium; RGM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Mycobacterium / drug effects*
  • Rifamycins / chemical synthesis
  • Rifamycins / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Rifamycins