G protein-coupled receptor desensitization and trafficking are important regulators of opioid signaling that can dictate overall drug responsiveness in vivo. Furthermore, different μ-opioid (μOR) ligands lead to varying degrees regulation, presumably because distinct structural conformations conferred by agonist binding. For example, morphine binding produces a μOR with low affinity for β-arrestin proteins limited internalization, whereas enkephalin analogs promote robust both β-arrestins...

Structural modification of salvinorin A, the active component Salvia divinorum, has resulted in synthesis novel neoclerodane diterpenes with opioid receptor affinity and activity. We report this study a nonnitrogenous diterpene mu (13) that is an agonist at receptors. This represents identification structural class agonists.

A collection of Lyngbya bouillonii from Palmyra Atoll in the Central Pacific, a site several thousand kilometers distant all previous collections this chemically prolific species cyanobacterium, was found to contain two new cancer cell cytotoxins apratoxin family. The structures compounds, apratoxins F and G, were determined by 1D 2D NMR techniques combination with mass spectrometric methods. Stereochemistry explored using chromatographic analyses hydrolytically released fragments optical...

Tropical parasitic and infectious diseases, such as leishmaniasis, pose enormous global health threats, but are largely neglected in commercial drug discovery programs. However, the Panama International Cooperative Biodiversity Group (ICBG) has been working to identify novel treatments for malaria, Chagas' disease, leishmaniasis through an investigation of plants microorganisms from Panama. We have pursued activity-guided isolation extract Lyngbya majuscula that was found be active against...

Four unsaturated polyketide lactone derivatives, coibacins A-D, were isolated from a Panamanian marine cyanobacterium, cf. Oscillatoria sp. The two different types of termini observed in these co-occurring metabolites, either methyl cyclopropyl ring as seen curacin A or vinyl chloride similar to that the jamaicamides, suggest an intriguing flexibility "beta branch" forming biosynthetic process. possess selective antileishmanial activity well potent anti-inflammatory activity.

Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation two new, veraguamide O ( 1 ) P 2 ), one known, C( 3 analogs isolated from cyanobacterial collection made Las Perlas Archipelago Panama. We hypothesized that these compounds would be cytotoxic cancer cell lines. The were screened against HEK-293, estrogen receptor positive (MCF-7), triple-negative breast...

Marine cyanobacteria have gained momentum in recent years as a source of novel bioactive small molecules. This paper describes the structure elucidation and pharmacological evaluation two new (veraguamide O (1) veraguamide P (2)) one known C (3)) analogs isolated from cyanobacterial collection made Las Perlas Archipelago Panama. We hypothesized that these compounds would be cytotoxic cancer cell lines. The were screened against HEK-293, estrogen receptor positive (MCF-7), triple-negative...

Rationale and Objective: The pain–depression dyad is highly prevalent has reciprocal psychological behavioral effects, leading to poor quality of life, increased disability, challenging therapeutic outcomes. In an attempt find better substances that can target comorbidity, we examined the effect aqueous (AE) ethanol (EE) extracts from Acacia sieberiana ( A. ) stem bark on reserpinized mice (female male Swiss albino aged 2‐3 months). Methods: was induced with 3 injections (Days 1–3) reserpine...

Salvinorin A, a potent hallucinogen isolated from the leaves of Salvia divinorum, has gained popularity among adolescents in USA. No detailed study pharmacokinetics been conducted vivo. The present investigates vivo salvinorin A (0.032 mg/kg, i.v. bolus) rhesus monkeys (n = 4, 2 male, female). elimination t1/2 was rapid (56.6 ± 24.8 min) for all subjects. Pharmacokinetic differences (distribution t1/2, and AUC) were observed between males females, suggesting potential sex its pharmacologic...

Salvinorin A [(2<i>S</i>,4<i>aR</i>,6<i>aR</i>,7<i>R</i>,9<i>S</i>,10<i>aS</i>,10<i>bR</i>)-9-(acetyloxy)-2-(3-furanyl)-dodecahydro-6<i>a</i>,10<i>b</i>-dimethyl-4,10-dioxo-2<i>h</i>-naphtho[2,1-<i>c</i>]pyran-7-carboxylic acid methyl ester] is a hallucinogenic κ-opioid receptor agonist that lacks the usual basic nitrogen atom present in other known opioid ligands. Our first published studies indicated weakly inhibited μ-receptor binding, and subsequent experiments revealed partially...

Salvinorin A is a psychoactive natural product that has been found to be potent and selective κ opioid receptor agonist in vitro vivo. The activity of salvinorin unusual compared other opioids such as morphine it mediates signaling yet leads less downregulation than observed with agonists. Our initial chemical modifications have yielded one analogue, herkinorin (1c), high affinity at the μOR. We recently reported 1c does not promote recruitment β-arrestin-2 μOR or internalization. Here we...

Fractionation of the extract marine cyanobacterium Lyngbya majuscula collected from Panama led to isolation malyngolide dimer (1). The planar structure 1 was determined using 1D and 2D NMR spectroscopy HRESI-TOFMS. absolute configuration established by chemical degradation followed chiral GC-MS analyses comparisons with an authentic sample seco-acid (4). Compound showed moderate in vitro antimalarial activity against chloroquine-resistant Plasmodium falciparum (W2) (IC(50) = 19 microM) but...

[reaction: see text] Two new neoclerodane diterpenes, salvinicins A (4) and B (5), were isolated from the dried leaves of Salvia divinorum. The structures these compounds elucidated by spectroscopic techniques, including (1)H (13)C NMR, NOESY, HMQC, HMBC. absolute stereochemistry was assigned on basis single-crystal X-ray crystallographic analysis salvinicin a 3,4-dichlorobenzoate derivative salvinorin B.

This study focused on the in vivo effects of κ-opioid hallucinogen salvinorin A, derived from plant <i>Salvia divinorum</i>. The A (0.0032–0.056 mg/kg i.v.) were studied a neuroendocrine biomarker assay anterior pituitary hormone prolactin gonadally intact, adult male and female rhesus monkeys (<i>n</i> = 4 each). Salvinorin produced dose- time-dependent effects, similar to synthetic high-efficacy κ-agonist U69,593 ((+)-(5α,7...

Abstract Previous studies established that Tyr‐ D ‐Ala‐Gly‐N‐Me‐Phe‐Gly‐ol (DAMGO) and (2 S ,4a R ,6a ,7 ,9 ,10a ,10b )‐9‐(Benzoyloxy)‐2‐(3‐furanyl)dodecahydro‐6a,10b‐dimethyl‐4,10‐dioxo‐2 H ‐naphtho‐[2,1‐ c ]pyran‐7‐carboxylic acid methyl ester (herkinorin) are fully efficacious μ ‐agonists. Herkinorin (HERK), unlike DAMGO, does not recruit β‐arrestin promote ‐receptor internalization, even in cells over express β‐arrestin. We hypothesized chronic HERK DAMGO treatment will differentially...

Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently been shown to possess opioid receptor activity in vitro vivo. To explore the structure−affinity relationships of this interesting class compounds, we synthesized a series analogues from 1 isolated Salvia divinorum. Here, report semisynthesis neoclerodane diterpenes their at receptors. This work will allow further development novel ligands.

Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and first example of non-nitrogenous opioid receptor ligand. At present, there little information as to why this compound selective for κ receptors. One approach better understanding mode binding 1 at receptors systematically alter structure examine effects on affinity activity. Currently, paucity methods described preparation analogues derived 1. Here, we report...