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

• Published in: Marine drugs Vol. 17; no. 9; p. 496
• Main Authors: Zhidkov, Maxim E, Smirnova, Polina A, Tryapkin, Oleg A, Kantemirov, Alexey V, Khudyakova, Yuliya V, Malyarenko, Olesya S, Ermakova, Svetlana P, Grigorchuk, Valeria P, Kaune, Moritz, Amsberg, Gunhild von, Dyshlovoy, Sergey A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.08.2019; MDPI
• Subjects: 14-bromoreticulatine; 3,10-dibromofascaplysin; Alkaloids; Alkaloids - chemical synthesis; Alkaloids - pharmacology; Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antibiotics; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis; Bio-assays; bioactivity; Bioassays; Breast cancer; Bromination; Cancer; Cell cycle; Cell Line, Tumor; Cell membranes; Cells; Chemistry Techniques, Synthetic - methods; Colon; Colon cancer; Communication; Cyclin-dependent kinases; Cytotoxicity; Drug Screening Assays, Antitumor; Halogenation; Humans; Indoles - chemical synthesis; Indoles - pharmacology; Kinases; Marine invertebrates; Melanoma; Microbial Sensitivity Tests; Porifera - chemistry; Prostate cancer; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; total synthesis; Toxicity; 3,10-dibromofascaplysin; total synthesis; bioactivity; 14-bromoreticulatine
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md17090496

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 ) 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.