Structure-Activity Relationships of Thiophene Carboxamide Annonaceous Acetogenin Analogs: Shortening the Alkyl Chain in the Tail Part Significantly Affects Their Growth Inhibitory Activity against Human Cancer Cell Lines

Chem Pharm Bull (Tokyo). 2021;69(10):1029-1033. doi: 10.1248/cpb.c21-00450.

Abstract

In a previous study, we found that the thiophene carboxamide solamin analog, which is a mono-tetrahydrofuran annonaceous acetogenin, showed potent antitumor activity through the inhibition of mitochondrial complex I. In this study, we synthesized analogs with short alkyl chains instead of the n-dodecyl group in the tail part. We evaluated their growth inhibitory activities against human cancer cell lines. We found that the alkyl chain in the tail part plays an essential role in their activity.

Keywords: annonaceous acetogenin; antitumor agent; organic synthesis; structure–activity relationship.

MeSH terms

  • Acetogenins / chemical synthesis
  • Acetogenins / chemistry
  • Acetogenins / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • Acetogenins
  • Antineoplastic Agents