Doubly prenylated tryptamines: cytotoxicity, antimicrobial activity and cyclisation to the marine natural product flustramine A.
The marine natural product flustramine A was synthesised via oxidative cyclisation of Nb-methylated 1-prenyl-2-tert-prenyl-6-bromotryptamine and subsequent reduction of the resulting amidinium salt. Only the tert-prenyl group migrated, whereas the 1-prenyl group remained in place. Interestingly, the 2-tert-prenylated precursor revealed to be the biologically most active of our entire series of 21 compounds. Required for cytotoxicity and antimicrobial activity was the presence of a non-cyclised tryptamine side chain carrying a free secondary amine, whereas the presence of a 6-bromo substituent did not enhance cytotoxicity. In a panel of 42 human tumor cell lines, most sensitive were the lung and mammary cancer cell lines LXFA629L (IC50 1.9 μM) and MAXF401NL (IC50 2.4 μM), respectively. In a serial dilution assay, satisfying IC50 values of 5.9 μM against Micrococcus luteus and 7.7 μM each against Mycobacterium phlei were determined for Nb-methyl-1-prenyl-2-tert-prenyl-6-bromotryptamine.
Institute of Organic Chemistry, TU Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
Santosh Kumar
SK
Adla
Florenz
F
Sasse
Gerhard
G
Kelter
Heinz-Herbert
HH
Fiebig
Thomas
T
Lindel
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008826:Microbial Sensitivity Tests; D016982:Micrococcus luteus / Q000187:drug effects*; D015394:Molecular Structure; D009168:Mycobacterium phlei / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001688:Biological Products; D026121:Indole Alkaloids; D014363:Tryptamines; C041253:flustramine A