Total Synthesis and Antibacterial Study of Cyclohexapeptides Desotamide B, Wollamide B and Their Analogs

Chem Biodivers. 2018 Jan;15(1). doi: 10.1002/cbdv.201700414. Epub 2017 Dec 27.

Abstract

As natural-product-derived antibiotics, desotamides A - D and wollamides exhibit growth inhibitory activity against Gram-posivite bacteria (IC50 0.6 - 7 μm) and are noncytotoxic to mammalian cells (IC50 > 30 μm). Herein we firstly report the total synthesis of above two cyclohexapeptides as well as a series of structural variants through solid phase peptide synthesis, of which 3 displayed a 2-fold increase of antibacterial activity when compared with the original peptide 1. This strategy may offer good improvements for the synthesis of other cyclic peptides.

Keywords: SPPS; Antibacterial activity; Desotamides; Total synthesis; Wollamides.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / growth & development
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis
  • Peptides, Cyclic / chemistry
  • Peptides, Cyclic / pharmacology*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Peptides, Cyclic
  • desotamide B
  • wollamide B