title: A Hexacyclic, Iboga-Derived Monoterpenoid Indole with a Contracted Tetrahydroazepine C-Ring and Incorporation of an Isoxazolidine Moiety, a Seco-Corynanthean, an Aspidosperma-Aspidosperma Bisindole with Anticancer Properties, and the Absolute Configuration of the Pyridopyrimidine Indole Alkaloid, Vernavosine.
abstract: Examination of the EtOH extract of the Malayan Tabernaemontana corymbosa resulted in the isolation of three new alkaloids, viz., cononuridine (1), an unusual hexacyclic, iboga-derived, monoterpenoid indole characterized by contraction of the tetrahydroazepine C-ring and incorporation of an additional isoxazolidine ring, taberisidine (2), a seco-corynanthean alkaloid, and conofolidine (3), an Aspidosperma-Aspidosperma bisindole that showed pronounced in vitro growth inhibitory activity against an array of human cancer cell lines, including KB, vincristine-resistant KB, PC-3, LNCaP, MCF7, MDA-MB-231, HT-29, and HCT 116 cells. The structures and absolute configurations of 1 and 3 and the absolute configuration of the novel pyridopyrimidine indole alkaloid vernavosine (4) were confirmed by X-ray diffraction analysis. A reasonable biosynthesis route to cononuridine starting from an iboga precursor is presented.
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Choy-Eng
authors.initials: CE
authors.lastname: Nge
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Kae-Shin
authors.initials: KS
authors.lastname: Sim
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Siew-Huah
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Noel F
authors.initials: NF
authors.lastname: Thomas
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Yun-Yee
authors.initials: YY
authors.lastname: Low
authors.affiliation: Department of Chemistry and ‡Institute of Biological Sciences, University of Malaya , 50603 Kuala Lumpur, Malaysia.
authors.forename: Toh-Seok
authors.initials: TS
authors.lastname: Kam
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D030009:Aspidosperma / Q000737:chemistry; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007624:KB Cells; D015394:Molecular Structure; D039821:Monoterpenes / Q000302:isolation & purification / Q000494:pharmacology; D030014:Tabernaemontana / Q000737:chemistry; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; D039821:Monoterpenes; C000594872:corynanthean; C000600318:vernavosine; D014750:Vincristine