Cytotoxic lignans from fruits of Cleistanthus tonkinensis.

Seven new lignans, cleistonkinins A- E (1-5), cleistonkisides A and B (6-7) were isolated from the fruits of Cleistanthus tonkinensis (Euphorbiaceae), together with five known aryltetralin lignans, cleisindoside B (8), cleistantoxin (9), cleisindoside D (10), neocleistantoxin (11) and polygamain (12). Their structures were established from spectral analysis, including mass spectrometry and 2D-NMR. The absolute configurations of 4-7 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 6 had selective inhibition with moderate cytotoxicity against Pan C1 and A549 cell lines, respectively. Cleistantoxin (9) was significantly active against A549, HeLa, Hep3B, Pan C1 and MCF7 cell lines while it was less cytotoxic against HeLa cells. Neocleistantoxin (11) exhibited remarkable inhibition toward A549, HeLa, MCF7 and Pan C1. This is the first report for cytotoxicity of 9 and 11 against A549, Hep3B and Pan C1 cell lines.

Cytotoxic Phenolic Compounds from Fruit Glandular Trichomes of Macaranga tanarius.

A new flavonoid, macatanarin D (1), together with five known stilbenes (2-6), was isolated from fruit glandular trichomes of Macaranga tanarius. Their structures were elucidated on the basis of spectroscopic methods and through comparison with data reported in the literature. All isolated compounds were evaluated for their cytotoxic activities against KB and MCF-7 cell lines. Compounds 3, 4, and 5 showed the strongest activities against both cell lines with IC50 values in the range of 0.03-0.12 µM, and compound 2 only showed a significant cytotoxicity against KB cell line (IC50 = 0.26 µM) and a moderate cytotoxicity against MCF-7 (IC50 = 10.4 µM). Compounds 1 and 6 showed weak cytotoxic activities against KB cell line with IC50 values of 29.3 and 24.7 µM, respectively.

Two new linear acetogenins from the fruits of Goniothalamus gracilipes.

Two new linear acetogenins, gracilipin A (1) and methylsaccopetrin A (2) along with seven known compounds, saccopetrin A (3), 7,3',4'-trimethylquercetin (4), rhamnazin (5), casticin (6), isokanugin (7), melisimplexin (8) and 5-hydroxy-3,7-dimethoxy-3',4'-methylenedioxyflavone (9) were isolated from the fruits of Goniothalamus gracilipes Bân. Their structures were established by spectral analysis, such as mass spectrometry, 1D-NMR, 2D-NMR and circular dichroism (CD). Compounds 1 and 3 showed cytotoxic activity against KB cell line with IC50 values of 14.6 and 15.3 µM, respectively.

Design, synthesis and cytotoxicity of bengamide analogues and their epimers.

Starting from d-glycero-d-gulo-heptonic acid γ-lactone and amino acids, a number of diastereoisomeric bengamide analogues were synthesized. Optimization of the reaction conditions revealed that microwave irradiation assistance is a powerful method for the preparation of aminolactams, as well as for the coupling reactions of the lactone 5 with aminolactams. Cytotoxic activity evaluation against six cancer cell lines (KB, HepG2, LU1, MCF7, HL60, and Hela) demonstrated that the configuration of C-2' seems to be critical for the cytotoxic activity of compounds 8b (2'R) and 8a (2'S). Additionally, comparison of cytotoxicity of the protected acetonide compounds with that of their corresponding deprotected bengamide analogues suggested that the flexibility of the ketide side chain should be required for their cytotoxic activity.

Synthesis and biological evaluation of febrifugine analogues.

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

Cytotoxic steroidal alkaloids from Kibatalia laurifolia.

Four new steroids, 3-epi-gitingensine (1), N-acetylgitingensine (6), kibalaurifoline (7) and kibalaurifenone (8), along with the known paravallarine (2), 7α-hydroxyparavallarine (3), gitingensine (4), and N-methylgitingensine (5) were isolated from the leaves of Kibatalia laurifolia. Their structures were determined primarily from mass spectrometry and 2D NMR analyses. On the basis of the known absolute configurations of 2 and 4, the absolute configurations of the new compounds were proposed. Due to the structural relationships of compounds 1-8, a biosynthetic pathway was suggested. Compound 2 was cytotoxic to KB cells (IC50 12.8 µM), followed by 1 with IC50 21.2 µM.