Ibogan, tacaman, and cytotoxic bisindole alkaloids from tabernaemontana. Cononusine, an iboga alkaloid with unusual incorporation of a pyrrolidone moiety.
Six new indole alkaloids, viz., cononusine (1, a rare example of an iboga-pyrrolidone conjugate), ervaluteine (2), vincamajicine (3), tacamonidine (4), 6-oxoibogaine (5), and N(4)-chloromethylnorfluorocurarine chloride (6), and two new vobasinyl-iboga bisindole alkaloids, ervatensines A (7) and B (8), in addition to other known alkaloids, were isolated from the stem-bark extract of the Malayan Tabernaemontana corymbosa. The structures of these alkaloids were established on the basis of NMR and MS analyses and, in one instance (7), confirmed by X-ray diffraction analysis. Vincamajicine (3) showed appreciable activity in reversing multidrug resistance in vincristine-resistant KB cells (IC50 2.62 μM), while ervatensines A (7) and B (8) and two other known bisindoles displayed pronounced in vitro growth inhibitory activity against human KB cells (IC50 < 2 μM). Compounds 7 and 8 also showed good growth inhibitory activity against A549, MCF-7, MDA-468, HCT-116, and HT-29 cells (IC50 0.70-4.19 μM). Cell cycle and annexin V-FITC apoptosis assays indicated that compounds 7 and 8 inhibited proliferation of HCT-116 and MDA-468 cells, evoking apoptotic and necrotic cell death.
†School of Pharmacy, University of Nottingham Malaysia Campus, Jalan Broga, 43500 Semenyih, Selangor, Malaysia.
Kuan-Hon
KH
Lim
‡School of Pharmacy, Centre for Biomolecular Sciences, The University of Nottingham, University Park, Nottingham, Nottinghamshire NG72RD, U.K.
Vijay J
VJ
Raja
‡School of Pharmacy, Centre for Biomolecular Sciences, The University of Nottingham, University Park, Nottingham, Nottinghamshire NG72RD, U.K.
Tracey D
TD
Bradshaw
§Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Siew-Huah
SH
Lim
§Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Yun-Yee
YY
Low
§Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Toh-Seok
TS
Kam
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D007624:KB Cells / Q000187:drug effects; D008296:Malaysia; D015394:Molecular Structure; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D030014:Tabernaemontana / Q000737:chemistry*; D014750:Vincristine / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; D007211:Indoles; D011760:Pyrrolidinones; C520379:tacaman; D014750:Vincristine