Dionisio Olmedo

3-Phenylcoumarins as Inhibitors of HIV-1 Replication

We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC50 values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.

A New Larvicidal Lignan from Piper fimbriulatum

Abstract A new lignan, 3,4,5′-trimethoxy-3′,4′-methylenedioxy-7,9′:7′,9 diepoxylignan (1) (6-[4-(3,4-dimethoxy-phenyl)-tetrahydro-furo[3,4-c.]furan-1-yl]-4-methoxy-benzo[] dioxole) together with two known lignans, 7′-epi.-sesartemin (2) and diayangambin (3), and a known flavonoid, 5-hydroxy-7,4′-dimethoxyflavone (4), were isolated from the leaves of Piper fimbriulatum. C. DC. Their structures were assigned by a combination of one- and two-dimensional NMR techniques. 7′-epi.-Sesartemin (2) showed the highest larvicidal activity against Aedes aegypti. (LC100 17.6 µg/ml) and weak antiplasmodial (IC50 7.0 µg/ml) and antitrypanosomal (IC50 39.0 µg/ml) activities. None of the compounds was active against Leishmania mexicana..

A New Cytotoxic Friedelane Acid - Pluricostatic Acid - and Other Compounds from the Leaves of Marila pluricostata

Bioassay-guided fractionation of the dichloromethane extract of the leaves of Marila pluricostata led to the isolation of 2α,3β-dihydroxy-D:A-friedoolean-28-oic acid (pluricostatic acid), a new friedelane triterpenoid, (1), ten known triterpenoids and three sterols. Their chemical structures were elucidated through spectroscopic analysis. The less polar fractions, on GC/MS analysis and comparison with a MS library, resulted in the identification of twenty four sesquiterpenoids. The new triterpenoid acid 1 showed cytotoxicity against the MCF-7, H-460, and SF-268 human cancer cell lines with GI50 values from 1.2 to 3.3 μg/mL.

Vasoactive effects of different fractions from two Panamanians plants used in Amerindian traditional medicine

ETHNOPHARMACOLOGICAL RELEVANCE Cecropia obtusifolia (Cecropiaceae) and Psychotria poeppigiana (Synonym: Cephaelis elata, Rubiaceae) are two Latin American plants broadly used in traditional Amerindian medicine. The former, together with many other species of the genus Cecropia, share the folk reputation of curing heart failure, cough, asthma and bronchitis. The latter is used in Panama by Kuna and Ngäbe Buglé (Guaymies) native Indians for the treatment of dyspnea. AIM OF THE STUDY Based on screening of selected medicinal Panamanian plants by radioligand-binding techniques by Caballero-George et al. (2001), the present study was carried out in order to investigate the vasoactive effects of different fractions from both P. poeppigiana and C. obtusifolia on rat thoracic aorta and identify active fractions and their chemical constituents. MATERIALS AND METHODS Both acid and neutral methanol fractions (P-AMeOH and P-NMeOH) and acid and neutral dichlorometane fractions (P-ADCM and P-NDCM) were obtained from P. poeppigiana crude methanolic and dichlorometane extracts, respectively. Identical fractionation was carried out for C. obtusifolia (C-AMeOH, C-NMeOH, C-ADCM and C-NDCM. Vasorelaxant effect of all fractions, and their inhibition of contractile responses to angiotensin II were evaluated in isolated aortic rings. RESULTS P-AMeOH, P-NMeOH and P-ADCM fractions induced a concentration-dependent relaxation (43.9+/-1.8%, 35.3+/-4.7% and 52.9+/-3.5%, respectively) in the endothelium-intact aorta precontracted by phenylephrine (PE, 10(-6)M). The relaxation produced by C-AMeOH and C-NMeOH (57.3+/-2.5% and 53.3+/-3.3%, respectively) was greater than the effect produced by C-ADCM and C-NDCM (42.2+/-3.4% and 21.8+/-0.8%, respectively). Only the incubation of the aortic rings with P-AMeOH reduced the maximum contraction induced by angiotensin II at 20.08+/-0.55%. CONCLUSIONS The direct vasorelaxation effect observed could explain in part the ethnomedical use of these plants in Amerindian traditional medicine. The most active fractions contain phenolic and aromatic acid compounds. Furthermore, P-AMeOH, the only fraction that showed both vasorelaxant effect and inhibition of contractile responses to angiotensin II, is the most rich in aromatic acids compounds and the only one that contains scopoletin.

Cheminformatic characterization of natural products from Panama

In this work, we discuss the characterization and diversity analysis of 354 natural products (NPs) from Panama, systematically analyzed for the first time. The in-house database was compared to NPs from Brazil, compounds from Traditional Chinese Medicine, natural and semisynthetic collections used in high-throughput screening, and compounds from ChEMBL. An analysis of the “global diversity” was conducted using molecular properties of pharmaceutical interest, three molecular fingerprints of different design, molecular scaffolds, and molecular complexity. The global diversity was visualized using consensus diversity plots that revealed that the secondary metabolites in the Panamanian flora have a large scaffold diversity as compared to other composite databases and also have several unique scaffolds. The large scaffold diversity is in agreement with the broad range of biological activities that this collection of NPs from Panama has shown. This study also provided further quantitative evidence of the large structural complexity of NPs. The results obtained in this study support that NPs from Panama are promising candidates to identify selective molecules and are suitable sources of compounds for virtual screening campaigns.

A new coumarin from the fruits of Coutarea hexandra

A new 5-O-β-D-glucopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (1), together with four known compounds, one coumarin, 5-O-β-D-galactopyranosyl-4-(4-hydroxyphenyl)-7-methoxy-2H-chromen-2-one (2) and three cucurbitacins, 23,24-dihydrocucurbitacin F (3), 23,24-dihydro-25-acetylcucurbitacin F (4) and 2-O-β-D-glucopyranosyl-23,24-dihydrocucurbitacin F (5) have been isolated and characterised from the ethanol extract of Coutarea hexandra fruits. Their structures have been established by spectroscopic analysis (NMR and MS). Interpretation of the HMQC, HMBC, COSY-45 and NOESY experiments permitted us to establish stereochemistry of the natural products. All compounds were tested in cytotoxicity assays against the breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines.

Neoflavonoids as Inhibitors of HIV-1 Replication by Targeting the Tat and NF-κB Pathways

Twenty-eight neoflavonoids have been prepared and evaluated in vitro against HIV-1. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase reporter gene. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Seven 4-phenylchromen-2-one derivatives showed HIV transcriptional inhibitory activity but only the phenylchrome-2-one 10 inhibited NF-κB and displayed anti-Tat activity simultaneously. Compounds 10, 14, and 25, inhibited HIV replication in both targets at concentrations <25 μM. The assays of these synthetic 4-phenylchromen-2-ones may aid in the investigation of some aspects of the anti-HIV activity of such compounds and could serve as a scaffold for designing better anti-HIV compounds, which may lead to a potential anti-HIV therapeutic drug.

Parathesilactones and Parathesiquinones from Branches of Parathesis amplifolia.

Abstract Three new lactone derivatives, (3E.)-5,6-dihydroxy-3-(3-hydroxy-4-nonyl-5-oxofuran-2(5H.)-ylidene)-7-nonyl-1-benzofuran-2(3H.)-one (1), (3E.)-5,6-dihydroxy-3-(3-hydroxy-4-decyl-5-oxofuran-2(5H.)-ylidene)-7-decyl-1-benzofuran-2(3H.)-one (2), and (3E.)-5,6-dihydroxy-3-(3-hydroxy-4-undecyl-5-oxofuran-2(5H.)-ylidene)-7-undecyl-1-benzofuran-2(3H.)-one (3), denominated as parathesilactones A, B, C, respectively, and two new quinone derivatives, (2,7,8-trihydroxy-3,6-didecyldibenzo[b,d.]furan-1,4-dione (4) and (2,7,8-trihydroxy-3,6-dinonyldibenzo[b,d.]furan-1,4-dione) (5), denominated as parathesiquinones A, B, respectively, were isolated from the branches of Parathesis amplifolia. Lund. (Myrsinaceae). In addition, three known triterpenes, α.-amyrin (6), β.-amyrin (7), and bauerenol (8), and four known alkenylresorcinols, 5-pentadec-8-enyl resorcinol (9), 5-pentadec-10-enyl resorcinol (10), 5-heptadec-8-enyl resorcinol (11), and 5-heptadec-10-enyl resorcinol (12), were also isolated. The structure elucidation was achieved by means of MS, GC-MS, IR, 1H, 13C spectroscopy including Heteronuclear Multiple Quantum Coherence (HMQC), and Heteronuclear Multiple Bond Correlation (HMBC) techniques.

Antinociceptive and Anti-inflammatory Activities of Methanol Extract of Ormosia coccinea (Aubl.) Jacks in vivo

The present study was conducted to evaluate the antinociceptive and anti-inflammatory activities of methanol extract of rachis of Ormosia coccinea (Aubl.) Jacks (MEOC) using animal models of nociception and inflammation. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Oral administration of MEOC (500 mg/kg) produced significant (p < 0.05) antinociceptive effects when tested in mice using acetic acid-induced abdominal writhing test and on the inflammatory phase of the formalin test. It was also demonstrated that MEOC had no significant effect on the response latency time to the heat stimulus in the thermal model of the hot plate test. The anti-inflammatory activity of the extract was assessed using carrageenan, histamine and serotonin induced oedema in rat paw. The oral administration of MEOC showed maximum inhibition (64.29%) at 1 h on carrageenan edema, but it did not modify the edema induced by histamine and serotonin. The present results suggest that MEOC has a peripheral antinociceptive and anti-inflammatory action.