Synthesis and Structure-Activity Relationship Study of NBRI16716B, an Antitumor Natural Product

Chem Pharm Bull (Tokyo). 2015;63(6):463-8. doi: 10.1248/cpb.c15-00200.

Abstract

The total synthesis of NBRI16716B (2), a naturally occurring modulator of tumor-stroma interactions, was successfully achieved. Using this synthetic route, a dehydroxy analogue (21) and a derivative lacking the 5-hydroxy-3-methylpentenoyl side chain (22) became accessible. A preliminary structure-activity relationship study to unveil the structural requirements for selective inhibition of tumor cells cocultured with stromal cells revealed that both of the hydroxamate structures of 2 are indispensable, whereas the 5-hydroxy-3-methylpentenoyl side chain is not essential.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Biological Products / chemical synthesis
  • Biological Products / chemistry*
  • Biological Products / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diketopiperazines / chemical synthesis
  • Diketopiperazines / chemistry*
  • Diketopiperazines / pharmacology*
  • Humans
  • Neoplasms / drug therapy
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Biological Products
  • Diketopiperazines