Synthesis and biological evaluation of novel lipoamino acid derivatives

Bioorg Med Chem Lett. 2016 Jan 1;26(1):209-12. doi: 10.1016/j.bmcl.2015.10.086. Epub 2015 Nov 2.

Abstract

Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50=15.3-22.4μM) against the four cell lines tested.

Keywords: Amino acid; Antibiofilm activity; Antimicrobial activity; Fatty acid; Lipoamino acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemical synthesis
  • Amino Acids / chemistry*
  • Amino Acids / pharmacology*
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Biofilms / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fungi / drug effects
  • Gram-Positive Bacteria / drug effects
  • Hep G2 Cells
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Oleic Acids / chemical synthesis
  • Oleic Acids / chemistry*
  • Oleic Acids / pharmacology*
  • Structure-Activity Relationship
  • Thioglycolates / chemistry

Substances

  • Amino Acids
  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antineoplastic Agents
  • Oleic Acids
  • Thioglycolates
  • methyl oleate
  • 2-mercaptoacetate