Synthesis of New Cyclomarin Derivatives and Their Biological Evaluation towards Mycobacterium Tuberculosis and Plasmodium Falciparum

Chemistry. 2019 Jul 2;25(37):8894-8902. doi: 10.1002/chem.201901640. Epub 2019 Jun 6.

Abstract

Cyclomarins are highly potent antimycobacterial and antiplasmodial cyclopeptides isolated from a marine bacterium (Streptomyces sp.). Previous studies have identified the target proteins and elucidated a novel mode of action, however there are currently only a few studies examining the structure-activity relationship (SAR) for both pathogens. Herein, we report the synthesis and biological evaluation of 17 novel desoxycyclomarin-inspired analogues. Optimization via side chain modifications of the non-canonical amino acids led to potent lead structures for each pathogen.

Keywords: Mycobacterium tuberculosis; Plasmodium falciparum; malaria; multiple-drug-resistance; tuberculosis.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology
  • Inhibitory Concentration 50
  • Mycobacterium tuberculosis / drug effects*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Plasmodium falciparum / drug effects*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antimalarials
  • Oligopeptides
  • Peptides, Cyclic
  • cyclomarin A

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