Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2421-4. doi: 10.1016/j.bmcl.2015.03.086. Epub 2015 Apr 4.

Abstract

There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs.

Keywords: Andrographolide; Cytotoxic activity; SAR; ent-Labdane diterpene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Drug Discovery
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Diterpenes
  • andrographolide