Simalikalactone D, a Potential Anticancer Compound from Simarouba tulae, an Endemic Plant of Puerto Rico.

Species of the genus Simarouba have been studied because of their antimalarial and antileukemic activities. A group of oxygenated terpenes called quassinoids have been isolated from species of the Simarouba genus, and are responsible for its therapeutic properties. We hypothesized that Simarouba tulae, an endemic plant from Puerto Rico, is a natural source rich in quassinoid compounds with anticancer activity. The leaves were processed and extracted with solvents of different polarities. The extracts were screened for their antiproliferative activity, and it was shown that the chloroform extract was the most active extract. This extract was purified using different chromatographic techniques to afford the quassinoid simalikalactone D (SKD). This compound was further characterized using NMR and X-ray diffraction analysis. A reassessment of original structural assignments for SKD is proposed. SKD showed high cytotoxicity activity, with an IC50 of 55, 58, and 65 nM in A2780CP20 (ovarian), MDA-MB-435 (breast), and MDA-MB-231 (breast) cell lines, respectively. Exposure to SKD led to 15% inhibition of the migration of MDA-MB-231 cells.

Corallolides A and B: bioactive diterpenes featuring a novel carbon skeleton.

Corallolides A (1) and B (2) are naturally occurring diterpenes isolated from the Caribbean gorgonian octocoral Pseudopterogorgia bipinnata collected near Providencia Island, Colombia. Their tricyclic structures are based on a uniquely substituted bicyclo[9.2.1]tetradecane ring system that was established through detailed spectroscopic analysis. Compounds 1 and 2 were shown to exhibit antiparasitic and antituberculosis activity, respectively.

Bioactive compounds from the gorgonian Briareum polyanthes. Correction of the structures of four asbestinane-type diterpenes.

Our extended chemical investigation of the crude MeOH-CHCl3 extract of the gorgonian octocoral Briareum polyanthes from Puerto Rico has led to the isolation of three eunicellin-type diterpenoids, 1-3, along with five (4-8) diterpenoids of the asbestinane-type and one (9) of the briarane-type of polycyclized diterpenes. The structures and relative stereochemistry of the new compounds 1-9 were established on the basis of spectroscopic analysis (1H NMR, 13C NMR, HMQC, HMBC, NOESY). The biological activity of these compounds against pathogenic microbes responsible for various human infectious diseases was investigated. In addition, new data recorded for four known asbestinin diterpenes also isolated during this investigation and further analysis through chemical reactions have prompted us to revise our original structural assignments for these compounds.

Caucanolides A-F, unusual antiplasmodial constituents from a colombian collection of the gorgonian coral Pseudopterogorgia bipinnata.

Six new diterpenoids, caucanolides A-F (1-6), have been isolated from extracts of the gorgonian octocoral Pseudopterogorgia bipinnata collected near the Colombian Southwestern Caribbean Sea. The structures of 1-6 were elucidated by comprehensive analysis of spectroscopic data. The caucanolides showed in vitro antiplasmodial activity against the malaria parasite, Plasmodium falciparum. In addition to possessing structures based on novel carbon skeletons, one of these metabolites, caucanolide B (2), constitutes the only example from nature of a secondary metabolite possessing the N(1),N(1)-dimethyl-N(2)-acylformamidine functionality.

Differential inhibition of nicotine- and acetylcholine-evoked currents through alpha4beta2 neuronal nicotinic receptors by tobacco cembranoids in Xenopus oocytes.

In tobacco, there are two types of compounds that interact with neuronal nicotinic acetylcholine receptors (nnAChRs) in the brain. The first is the addictive component of tobacco and an agonist of these receptors, nicotine. The second are cyclic diterpenoids called cembranoids that non-competitively inhibit many types of nnAChRs. Nictotinic receptors composed of alpha4beta2 subunits are the predominant type of nicotinic receptors in the brain. These alpha4beta2 receptors are up-regulated upon chronic exposure to nicotine and have been implicated in nicotine addiction. The present study was designed to determine whether the inhibitory effects of two cembranoids from tobacco [(1S, 2E, 4R, 6R, 7E, 11E)-2,7,11-cembratriene-4,6-diol (4R) and its diastereoisomer (1S, 2E, 4S, 6R, 7E, 11E)-2,7,11-cembratriene-4,6-diol (4S)] were comparable on acetylcholine (ACh) and nicotine-evoked currents through alpha4beta2 nnAChRs. alpha4beta2 nnAChRs from rat brain were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. The dose-response curves for acetylcholine and nicotine were hyperbolic and bell-shaped, respectively. Although there was no difference in the potency between cembranoids 4R and 4S, both of these cembranoids more potently inhibited nicotine-induced currents than acetylcholine-induced currents. Furthermore, both cembranoids were more potent inhibitors of this receptor when they were preincubated for 1 min prior to application of agonist. The finding that cembranoids preferentially inhibit nicotine-induced currents over those elicited by the natural neurotransmitter acetylcholine may have important implications when developing strategies to prevent nicotine addiction and tobacco use.

Briarellins J-P and polyanthellin A: new eunicellin-based diterpenes from the gorgonian coral Briareum polyanthes and their antimalarial activity.

A new chemical study of the hexane extract of the gorgonian Briareum polyanthes collected in Puerto Rico afforded 10 new diterpenes of the eunicellin class, briarellins 1-9 and polyanthellin A (10), along with the known diterpene briarellin D (11). The structures and relative stereochemistry of metabolites 1-10 were assigned on the basis of NMR studies, chemical methods, and comparisons to the spectral properties of 11. A reassessment of prior structural assignment for briarellin A and two known sclerophytin-type diterpenes, 13 and 14, is proposed. Antimalarial tests on 1-6 and 8-12 indicated that they were active against Plasmodium falciparum.