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.
Maxim E Zhidkov  1 ,  Polina A Smirnova  2 ,  Oleg A Tryapkin  2 ,  Alexey V Kantemirov  2 ,  Yuliya V Khudyakova  3 ,  Olesya S Malyarenko  3 ,  Svetlana P Ermakova  3 ,  Valeria P Grigorchuk  4 ,  Moritz Kaune  5 ,  Gunhild von Amsberg  5  6 ,  Sergey A Dyshlovoy  2  3  5  6
Affiliations
  • 1. Department of organic chemistry and Laboratory of biologically active compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia. [email protected].
  • 2. Department of organic chemistry and Laboratory of biologically active compounds, School of Natural Sciences, Far Eastern Federal University, 8 Sukhanov Str., Vladivostok 690950, Russia.
  • 3. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, 159 Prospekt 100 Let Vladivostoku, Vladivostok 690022, Russia.
  • 4. Federal Scientific Center of the East Asia Terrestrial Biodiversity (Institute of Biology and Soil Science), Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-Let Vladivostoku, Vladivostok 690022, Russia.
  • 5. Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • 6. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany.
PMID: 31450717 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.
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