Toh-Seok Kam

Alkaloids from Kopsia griffithii

Nineteen alkaloids were isolated from the leaf extract of Kopsia griffithii, of which two were new, viz., 12-methoxypleiocarpine and the tetrahydro-β-carboline derivative, harmicine.

Lundurines A, B and C, new indole alkaloids with a novel carbon skeleton containing a cyclopropyl moiety

Abstract Three new indole alkaloids viz., Lundurines A, B and C, possessing a novel carbon skeleton incorporating a cyclopropyl unit were obtained from Kopsia tenuis. The structures of these alkaloids were elucidated by 2-D NMR methods.

Leishmanicidal alkaloids from Kopsia griffithii

Thirteen alkaloids were isolated from the stem-bark extract of Kopsia griffithii, of which three were new. These were the N(4)-oxides of akuammiline, 16-epi-deacetylakuammiline and 11,12-methylenedioxykopsinaline. Harmane, pleiocarpine and buchtienine showed antileishmanial activity.

Plumeran alkaloids from Kopsia profunda

Abstract Two new plumeran alkaloids, N -methoxycarbonyl-11,12-methylenedioxy-Δ 16,17 -kopsinine and N -methoxycarbonyl- 12-methoxy-Δ 16,17 -kopsinine, have been isolated from the stem of Kopsia profunda . The structures of these alkaloids were assigned by spectral methods.

Grandilodines A−C, Biologically Active Indole Alkaloids from Kopsia grandifolia

Three new indole alkaloids (1-3), named grandilodines A-C, and five known ones were obtained from the Malayan Kopsia grandifolia. The structures were established using NMR and MS analyses and, in the case of 1 and 2, were confirmed by X-ray diffraction analyses. Alkaloids 1, 3, and lapidilectine B (8) were found to reverse multidrug resistance in vincristine-resistant KB cells.

Bipleiophylline, an Unprecedented Cytotoxic Bisindole Alkaloid Constituted from the Bridging of Two Indole Moieties by an Aromatic Spacer Unit

A cytotoxic bisindole alkaloid possessing an unprecedented structure in which two indole moieties are bridged by an aromatic spacer unit has been isolated from Alstonia angustifolia. The structure was established by analysis of the spectroscopic data and confirmed by X-ray diffraction analysis. A possible biogenetic pathway from pyrocatechuic acid and pleiocarpamine is presented.

Pauciflorines A and B, novel melanin biosynthesis inhibitors from Kopsia

Abstract Two new pentacyclic indoles viz., Pauciflorines A and B from Kopsia pauciflora were found to exhibit potent inhibitory activity on melanin biosynthesis of cultutred B-16 melanoma cells.

Jerantinines A−G, Cytotoxic Aspidosperma Alkaloids from Tabernaemontana corymbosa

Seven new indole alkaloids of the Aspidosperma type, jerantinines A-G (1-7), were isolated from a leaf extract of the Malayan Tabernaemontana corymbosa. The structures were established using NMR and MS analysis. Five of the alkaloids isolated and two derivatives (1-5, 8, 9) displayed pronounced in vitro cytotoxicity against human KB cells (IC50 < 1 microg/mL).

Alkaloids from Kopsia dasyrachis

Abstract A total of 32 alkaloids were obtained from the stem extract of Kopsia dasyrachis,of which ten are new, viz., kopsiflorine N (4)-oxide, 11-methoxykopsilongine N (4)-oxide,kopsifine, decarbomethoxykopsifine, kopsinarine, 11,12-methylenedioxykopsine, dasyrachine,rhazinicine, (+)-19 (R)-hydroxyeburnamine and (−)-19 (R)-hydroxyisoeburnamine.

Induction of insulin production in rat pancreatic acinar carcinoma cells by conophylline.

We set up a screening system to detect low-molecular-weight compounds that induce insulin expression in pancreatic acinar carcinoma AR42J cells. They can differentiate into insulin-producing cells with neuron-like morphological change when treated with activin A. We employed this morphological change for the screening of beta-cell inducers among various signal transduction inhibitors. As a result, a vinca alkaloid, conophylline, induced neurite formation at 0.1 approximately 0.3 microg/ml in 72 h, like activin A. Conophylline-treated cells were found to express insulin as measured at both mRNA and protein levels. By RT-PCR analysis, conophylline-treated cells were shown to express neurogenin3 strongly. They also expressed Beta2/NeuroD and Nkx2.2, but not Pax4 and PP. Although activin A induces nuclear translocation of Smad2, conophylline did not. But the latter induced p38 activation, like activin A, as detected by phosphorylation. Pretreatment with a p38-specific inhibitor, SB203580, lowered the conophylline-induced insulin production. Therefore, p38 activation would be involved in the differentiation of AR42J cells into insulin-producing cells. Studies on structure-activity relationship with conophyllidine, conofoline, conophyllinine, and related monomer alkaloids showed that the dimeric aspidosperma structure with the dihydrofuran unit in its center was essential for the differentiation-inducing activity.