Synthesis and biological evaluation of analogues of cryptolepine, an alkaloid isolated from the Suriname rainforest.
Bioassay-guided fractionation of an extract of a mixture of Microphilis guyanensis and Genipa americanacollected in the rainforest of Suriname yielded the known alkaloid cryptolepine (2) as the major active compound in a yeast bioassay for potential DNA-damaging agents; the same compound was later reisolated from M. guyanensis. The structure of cryptolepine was identified unambiguously by spectral data and by its total synthesis. Several cryptolepine derivatives (3-29, 32-41) were synthesized based on modifications of the C-2, N-5, N-10, and C-11 positions. Two cryptolepine dimers (30, 31) were also prepared. The structure modifications did not result in compounds with a higher potency than the parent compound cryptolepine in the yeast assay system, although some derivatives did show significant activity. Selected compounds (6, 7, 17, 22, 23, 26, and 27) were also tested for cytotoxicity in mammalian cell culture, and two compounds showed significant cytotoxic activity.
Yang
S W
SW
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0212, USA.
Abdel-Kader
M
M
Malone
S
S
Werkhoven
M C
MC
Wisse
J H
JH
Bursuker
I
I
Neddermann
K
K
Fairchild
C
C
Raventos-Suarez
C
C
Menendez
A T
AT
Lane
K
K
Kingston
D G
DG
D000470:Alkaloids / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids; D007211:Indoles; D008826:Microbial Sensitivity Tests; D010946:Plants, Medicinal / Q000737:chemistry*; D011804:Quinolines; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D013532:Suriname; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000935:Antifungal Agents; D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; D007211:Indoles; D011804:Quinolines; C024015:cryptolepine