Biomedical subjects
Publications and source records attributed to Toh-Seok Kam.
[structure: see text] A new indole alkaloid, arboflorine, possessing a novel pentacyclic carbon skeleton and incorporating a third nitrogen atom was obtained from the Malayan Kopsia arborea. The structure was established by spectroscopic analysis, and a possible biogenetic pathway from a preakuammicine-type precursor is presented.
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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis in many transformed cells but not in normal cells and, hence, has emerged as a novel anticancer agent. Previously, we showed that although most adult T-cell leukemia/lymphoma (ATLL) cells express the TRAIL death receptor DR4 (TRAIL-R1) or DR5 (TRAIL-R2), they are resistant to TRAIL. Thus, in this study, we tried to find natural products that can overcome TRAIL resistance. Among more than 150 materials screened, a dihydroflavonol that was extracted from Blumea balsamifera (BB-1) exhibited the most striking synergism with TRAIL. Treatment of the TRAIL-resistant ATLL cell line KOB, with a combination of BB-1 and TRAIL, resulted in apparent apoptosis that was not observed on treatment with either agent alone. Furthermore, pretreatment with BB-1 followed by TRAIL further augmented the synergism. BB-1 increased the level of TRAIL-R2 promoter activity and surface protein expression in a p53-independent manner. TRAIL-R2 siRNA inhibited the synergism, indicating that sensitization was caused by the increase of TRAIL-R2 expression. More interestingly, similar effects were observed in other leukemia cell lines by exactly the same mechanisms. These results suggest that combined treatment with BB-1 and TRAIL may be a new strategy for cancer therapy.
A series of indole alkaloids of the ibogan-type was assessed for their cytotoxic effects as well as their potential in reversing MDR in vincristine-resistant KB cells. Of a total of 25 compounds tested, 3(S)-cyanocoronaridine, 3(S)-cyanoisovoacangine, 3(S)-cyanovoacangine, and 10,11-demethoxychippiine were found to show appreciable cytotoxicity toward KB cells, while coronaridine, heyneanine, 19-epi-heyneanine, dippinine B, and dippinine C, were found to reverse MDR in vincristine-resistant KB cells.
Six new indole alkaloids, viz., (3S)-3-cyanocoronaridine (2), (3S)-3-cyanoisovoacangine (3), conolobine A (5), conolobine B (6), conolidine (7), and (3R/3S)-3-ethoxyvoacangine (8), in addition to 36 known ones, were obtained from the stem-bark extract of the Malayan Tabernaemontana divaricata. The structures were determined by NMR and MS analysis. The CN-substituted alkaloids showed appreciable cytotoxicity towards the KB human oral epidermoid carcinoma cell-line.
Six new alkaloids, viz., alstolactone, affinisine oxindole, lagumicine, N(4)-demethylalstonerine, N(4)-demethylalstonerinal, and 10-methoxycathafoline N(4)-oxide, in addition to 36 other known alkaloids, were obtained from the leaf extract of Alstonia angustifolia var. latifolia. The structures of the new alkaloids were determined using NMR and MS analysis.
Two new venalstonine derivatives, viz., venacarpines A and B, and one new dioxokopsan derivative, kopsorinine, in addition to the kopsifolines A-F, and 11 other known alkaloids, were isolated from a Malayan Kopsia species. The structures of the new alkaloids were determined using NMR and MS analysis.
Ten new indole alkaloids, alstomaline (1), 10,11-dimethoxynareline (2), alstohentine (3), alstomicine (4), 16-hydroxyalstonisine (5), 16-hydroxyalstonal (6), 16-hydroxy-N(4)-demethylalstophyllal oxindole (7), alstophyllal (8), 6-oxoalstophylline (9), and 6-oxoalstophyllal (10), in addition to 21 other known ones, were obtained from the leaf extract of the Malayan Alstonia macrophylla. The structures were determined using NMR and MS analysis.
The ethanol extract of the leaves of Tabernaemontana divaricata (double flower variety) provided a total of 23 alkaloids, including the new aspidosperma alkaloids, taberhanine, voafinine, N-methylvoafinine, voafinidine, voalenine and the new bisindole alkaloid, conophyllinine in addition to the previously known, biologically active bisindole, conophylline and its congener, conofoline. The structures of the new alkaloids were established by spectroscopic methods. The preparation and characterization of the corresponding quinones of the biologically active bisindoles are also described in relation to a structure-activity study of these compounds with respect to their action in stimulating insulin expression.
Four bisindole alkaloids, viz., 19'(S)-hydroxyconodurine, conodurinine, 19'(S)-hydroxyconoduramine, and 19'(S)-hydroxyervahanine A, in addition to conodurine and ervahanine A, were obtained from the leaf and stem-bark extracts of Tabernaemontana corymbosa. The structures of the new alkaloids were determined using NMR and MS analysis.
Ten new bisindole alkaloids of the vobasinyl-ibogan type, viz., conodiparines A-F (1-6), conodutarines A and B (7, 8), and cononitarines A and B (9, 10), were obtained from the leaf extract of the Malayan species Tabernaemontana corymbosa. The structures were determined using NMR and MS analysis.
Five new indole alkaloids of the ibogan type (1-5), in addition to 12 other known iboga alkaloids, were obtained from the leaf and stem-bark extract of the Malayan species Tabernaemontana corymbosa, viz., 19(S)-hydroxyibogamine (1), 19-epi-isovoacristine (2), isovoacryptine (3), 3R/S-ethoxyheyneanine (4), and 3R/S-ethoxy-19-epi-heyneanine (5). The structures were determined using NMR and MS analysis and comparison with known related compounds.