Improved potency of Clofazimine derivatives against species.

Eur J Med Chem Rep

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.

Published: August 2024

AI Article Synopsis

  • Millions of infections resistant to antimicrobials cause over 700,000 deaths globally each year, especially from nontuberculosis mycobacteria and Gram-negative bacteria, which present treatment challenges due to multi-drug resistance.
  • Clofazimine (CFZ), commonly used for treating leprosy, has potential but limited research on its effectiveness against Gram-negative bacteria and is known for causing skin pigmentation as a side effect.
  • In this study, 11 CFZ analogues were developed and analyzed, revealing some with equal or better antibacterial activity than CFZ, marking a significant finding that could lead to safer alternative treatments.

Article Abstract

Globally, millions of infections that are resistant to antimicrobial agents are reported annually, leading to more than 700,000 fatalities. Among all, challenges arise particularly from nontuberculosis mycobacterial (NTM) and Gram-negative bacteria, as they exhibit limited treatment options in light of increasing reports of multi-drug resistant strains. Clofazimine (CFZ) is an antimycobacterial medication used to treat leprosy, and it is also known for its side effect of inducing skin pigmentation. The use of CFZ and its analogues against a broad range of Gram-negative bacteria has not been extensively investigated. In this study, we designed, synthesized and studied 11 CFZ analogues and identified examples with comparable or improved anti-bacterial activity relative to that of CFZ itself. This is the first report demonstrating activity of CFZ and its analogues against species. The results of these studies may facilitate the development of CFZ analogues with limited side effects in humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11218832PMC
http://dx.doi.org/10.1016/j.ejmcr.2024.100147DOI Listing

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