Total Syntheses and Preliminary Biological Evaluation of Brominated Fascaplysin and Reticulatine Alkaloids and Their Analogues

Mar Drugs. 2019 Aug 25;17(9):496. doi: 10.3390/md17090496.

Abstract

A simple approach toward the synthesis of the marine sponge derived pigment fascaplysin was used to obtain the marine alkaloids 3-bromofascaplysin and 3,10-dibromofascaplysin. These compounds were used for first syntheses of the alkaloids 14-bromoreticulatate and 14-bromoreticulatine. Preliminary bioassays showed that 14-bromoreticulatine has a selective antibiotic (to Pseudomonas aeruginosa) activity and reveals cytotoxicity toward human melanoma, colon, and prostate cancer cells. 3,10-Dibromofascaplysin was able to target metabolic activity of the prostate cancer cells, without disrupting cell membrane's integrity and had a wide therapeutic window amongst the fascaplysin alkaloids.

Keywords: 14-bromoreticulatine; 3,10-dibromofascaplysin; bioactivity; total synthesis.

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / pharmacology*
  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Chemistry Techniques, Synthetic / methods
  • Drug Screening Assays, Antitumor
  • Halogenation
  • Humans
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Microbial Sensitivity Tests
  • Porifera / chemistry*
  • Pseudomonas aeruginosa / drug effects

Substances

  • Alkaloids
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Indoles
  • fascaplysine