Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells

Bioorg Med Chem Lett. 2015 Feb 1;25(3):435-7. doi: 10.1016/j.bmcl.2014.12.061. Epub 2014 Dec 24.

Abstract

The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity.

Keywords: 4-Amino-4-dehydroxylarctigenin; Arctigenin (ATG); Bioisosterism; Glucose starvation; Natural product.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / toxicity
  • Antineoplastic Agents, Phytogenic / chemical synthesis*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / toxicity
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Furans / chemistry*
  • Furans / toxicity
  • Glucose / pharmacology
  • Humans
  • Lignans / chemical synthesis*
  • Lignans / chemistry
  • Lignans / toxicity
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Furans
  • Lignans
  • Glucose
  • 4-Butyrolactone
  • arctigenin