High-Content Screening Pipeline for Natural Products Targeting Oncogenic Signaling in Melanoma.

The incidence of melanoma, the most fatal dermatological cancer, has dramatically increased over the last few decades. Modern targeted therapy with kinase inhibitors induces potent clinical responses, but drug resistance quickly develops. Combination therapy improves treatment outcomes. Therefore, novel inhibitors targeting aberrant proliferative signaling in melanoma via the MAPK/ERK and PI3K/AKT pathways are urgently needed. Biosensors were combined that report on ERK/AKT activity with image-based high-content screening and HPLC-based activity profiling. An in-house library of 2576 plant extracts was screened on two melanoma cell lines with different oncogenic mutations leading to pathological ERK/AKT activity. Out of 140 plant extract hits, 44 were selected for HPLC activity profiling. Active thymol derivatives and piperamides from Arnica montana and Piper nigrum were identified that inhibited pathological ERK and/or AKT activity. The pipeline used enabled an efficient identification of natural products targeting oncogenic signaling in melanoma.

Pharmacognostic Evaluation of Ten Species of Medicinal Importance of Cecropia: Current Knowledge and Therapeutic Perspectives.

This work covers a systematic review of literature about the genus Cecropia from 1978 to 2020, emphasizing the analysis of 10 of the most relevant species and their associated biological activities. Cecropia is a neotropical genus, which comprises about 61 native species in the American continent where it is known to be part of the traditional medicine of numerous countries. Secondary metabolites described for this genus showed an elevated structural and functional diversity, where polyphenols have been the most abundant. Based on this diversity, Cecropia phytochemicals represent an important source of potential therapeutic agents yet to be exploited. This review also highlights the effectiveness of combining chemometrics and ultra-performance liquid chromatography-tandem mass spectrometry as a novel approach to successfully single out Cecropia species phytochemicals. While the medicinal use of Cecropia species is officially recognized in National Pharmacopoeias and Formularies of several Latin American countries, it is important to recognize that these phytomedicines are complex mixtures requiring a thorough understanding of their chemical composition and their correlation with biological activities to guarantee their quality, safety, and efficacy.

Assessment of the antinociceptive and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea.

Context: Since there is still a great need to search for plant species with antinociceptive and anti-inflammatory activities, Diploptropis purpurea (Rich.) Amshoff (Fabaceae) is studied for the first time. Objective: This evaluates the analgesic and anti-inflammatory activities of the stem methanol extract of Diplotropis purpurea (MEDP). Material and methods: The anti-inflammatory and analgesic effects of MEDP of D. purpurea were evaluated in vivo. The antinociceptive activity was assessed in CD1 male mice were treated by oral gavage with 500 mg/kg of MEDP 30 min before submitting to acetic acid-induced abdominal writhing, hot-plate, and formalin tests. Paws oedema induced by carrageenan, histamine or serotonin were performed in male Sprague-Dawley rats to determinate the anti-inflammatory activity. Results: Oral administration of MEDP produced significant antinociceptive effects on the inflammatory phase in the formalin test [12.0 s versus 72.5 s in carboxymethyl cellulose (CMC) control group]. MEDP produced an analgesic effect in the hot-plate model, although the effect was modest compared to tramadol (40 and 60%, respectively). The oral administration of MEDP in a dose of 500 mg/kg showed maximum inhibition (75.1%) after 0.5 h in carrageenan-induced oedema, but it did not modify histamine or serotonin-induced oedemas. Discussion and conclusion: In the peripheral nociception model, acetic acid-induced abdominal writhing, the MEDP did not show a protective effect, but its analgesic effects were evident in the inflammatory phase of the formalin test and in the hot-plate model. These results show that the anti-inflammatory effect was accompanied by a reduction in the perception of painful stimuli.

Ethnomedical uses and pharmacological activities of most prevalent species of genus Piper in Panama: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperaceae is the fifth largest family of plants in Panama. This review focuses on the ethnomedical uses of the most prevalent Panamanian species and biological activities of their extracts and/or constituents both in Panama and worldwide. Many species have a plethora of ethnomedical uses such as antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic, anti-Helicobacter pylori, antiulcer, antiprotozoal, estrogenic, insecticidal, local anesthetic, diuretic, and for women's health conditions. AIM OF THE REVIEW: The aim of this review is to compile all ethnomedical uses of most prevalent species of Piper in Panama, and their extracts or phytoconstituents worldwide, through a complete literature search, so that it may allow selection of potential unexplored Piper species for future research and development of phytotherapeuticals for important ailments. METHODOLOGY: This review conducted a thorough search in books and databases such as Google Scholar, PubMed, Sci-Finder, Scopus, ACS publications, Science Direct, and Reaxys (Elsevier), until October of 2017. The information provided in this review is based on peer-reviewed papers only in English. The key words used to search were: "Piper", "Piperaceae", "Panama", "Pharmacological activity", "Chemistry," "Toxicity," and "Clinical studies". Scientific names of the plants were validated through www.tropicos.org. Potential full-texts of eligible papers, irrespective of database, were identified. Study selection and data extraction were conducted by one author (AIS) and confirmed by others (MPG, ADA). The extracted data were summarized in tabular form and a narrative description was used to provide a summary of updated information. RESULTS: The ethnomedical uses of most prevalent 23 Panamanian species of Piper both in Panama as well in the world are provided. Of these species only Piper arboreum, Piper auritum, Piper cordulatum, Piper hispidum, Piper dariense, Piper multiplinervium and Piper umbellatum have ethnomedical uses in Panama. Some of the uses are by native Amerindians of Panama. These include ailments such as liver pains, common colds, skin infections, insecticidal, as a bath to alleviate colds, snakebites, different types of pains, skin ailments, wound healing, rheumatism, women's health, antipyretic, and anti-inflammatory. Other Panamanian species are widely used in many countries of the world. Of all the Piper species, P. aduncum has the most ethnomedical uses. Panamanian uses are different from the ones in other countries. A total of 61 compounds present in Piper species reported in this review have shown a variety of biological activities in vitro. These compounds belong to different chemical types, such as chromenes, amides, alkaloids, benzopyrans, benzoates, essential oils, pyrrolidines, flavokaines, chalcones, methylenedioxy propiophenones, cinnamates, monoterpenes, sesquiterpenes, phenols, among others. From this review it is evident that extracts and pure compounds isolated from Piper species have shown a wide array of mainly in vitro activity and some ethnomedical uses may be correlated with their activities reported. CONCLUSIONS: Plants of this genus have provided bioactive species, both from crude extracts and pure compounds thus substantiating their efficacy in traditional medicine. In vivo and toxicological studies are still limited, but the results of different activities of Piper reported point out the great potential of these species for obtaining bioactive principles that may be useful in treating diseases. However, a thorough investigation of Piper species relating to chemistry, in vivo pharmacological activities, with emphasis on their mechanism of action, safety and efficacy and toxicity is warranted.

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.

Chemical Composition and Biological Activity of Essential Oils from Different Species of Piper from Panama.

The chemical composition of leaf essential oils from 11 species of Piper from Panama was analyzed by a combination GC-FID and GC-MS procedures. Six of them had sesquiterpene hydrocarbons as major constituents, three were characterized by monoterpene hydrocarbons, one by a diterpene, and one by a phenylpropanoid, dillapiole. The main components identified in each species were: cembratrienol (25.4 %) in Piper augustum; ß-pinene (26.6 %) in Piper corrugatum; α-pinene (19.4 %) in Piper curtispicum; trans-ß-farnesene (63.7 %) in Piper darienense; p-cymene (43.9 %) in Piper grande; dillapiole (57.7 %) in Piper hispidum; linalool (14.5 %), α-phellandrene (13.8 %), and limonene (12.2 %) in Piper jacquemontianum; ß-caryophyllene (45.2 %) in Piper longispicum; linalool (16.5 %), α-phellandrene (11.8 %), limonene (11.4 %), and p-cymene (9.0 %) in Piper multiplinervium; ß-selinene (19.0 %), ß-elemene (16.1 %), and α-selinene (15.5 %) in Piper reticulatum; and germacrene D (19.7 %) in Piper trigonum. The essential oils of P. hispidum and P. longispicum at a concentration of 250 µg/mL showed larvicidal activity against Aedes aegypti, while the oils from P. curtispicum, P. multiplinervium, P. reticulatum, and P. trigonum were inactive (LC100 ≥ 500 µg/mL). The essential oils of P. grande, P. jacquemontianum, and P. multiplinervium showed no significant antifungal activity (MIC > 250 µg/mL) against several yeasts and filamentous fungal strains.

Chemical Adulterants in Herbal Medicinal Products: A Review.

Many herbal medicinal products have been found to contain synthetic prescription drugs as chemical adulterants. This has become evident by the number of toxicity cases and adverse reactions reported in which casualties were reported via analytical techniques that detected the presence of chemical adulterants in them, which could be responsible for their toxicity. The adulteration of herbal medicinal products with synthetic drugs continues to be a serious problem for regulatory agencies. This review provides up to date information on cases of toxicity, major chemical adulterants in herbal medicinal products, and current analytical techniques used for their detection.

Isolation of major components from the roots of Godmania aesculifolia and determination of their antifungal activities.

From the methanol root extract of Godmania aesculifolia, a species selected in a multinational OAS program aimed at discovering antifungal compounds from Latin American plants, a new chavicol diglycoside (1), the known 3,4-dihydroxy-2-(3-methylbut-2-en-1-yl)-3,4-dihydronaphthalen-1(2H)-one (2), and lapachol (3) were isolated and characterized by 1D and 2D NMR and MS techniques. Only 3 exhibited fairly good activity against a panel of clinical isolates of Cryptococcus neoformans (MIC50 between 7.8 and 31.2 µg/mL) and moderate activities against Candida spp. and non-albicans Candida spp.

Lycopodiaceae from Panama: a new source of acetylcholinesterase inhibitors.

Acetylcholinesterase (AChE) inhibitors have been used for the symptomatic treatment of Alzheimer's disease. Eleven whole plants from Panama belonging to the Lycopodiaceae family have been screened for their anticholinesterase inhibitory and antioxidant activities by a thin-layer chromatography (TLC) bioautography method. Of these, only Lycopodium clavatum subsp. clavatum showed strong AChE inhibition. Seven plant extracts showed moderate inhibition, two of them, Huperzia cf chamaeleon and Huperzia reflexa, also possessed an antioxidant activity. This is the first report of anticholinesterase and antioxidant activities in these two native plants. Additionally, alkaloid extracts of the Lycopodiaceae plants were also analysed by TLC and LC-MS to identify the well-known AchE inhibitor, huperzine A. Two plants, H. cf chamaeleon and H. reflexa var. minor, showed the presence of huperzine.

Two new alkylresorcinols from Homalomena wendlandii and their cytotoxic activity.

In the course of our search for antineoplasic agents from Panamanian Flora, two new alkylresorcinols: 1-(2,6-dihydroxyphenyl)octan-l-one (1) and (+)-1-(3-(1-(2,6-dihydroxyphenyl)butyl)-2,6-dihydroxyphenyl)octan-l-one (2), together with three known compounds, (1R, 2R)-l-(benzo[d][1,3]dioxol-5-yl)propane-1,2,3-triol (3), (+)-aptosimon (4) and (-)-sesamin (5), were identified from the leaves of Homalomena wendlandii Schott (Araceae). Their structures were established by 1D and 2D NMR and IR spectroscopic, and MS methods. Compound 2 exhibited IC50 values of 3.3, 5.8 and 4.0 microg/mL against MCF-7, SF-268 and H-460 cancer human cell lines, respectively.

El fruto de noni (Morinda Citrifolia L) / Noni fruit (Morinda citrofolia L)

Las hojas y especialmente los frutos de noni (Morinda citrofolia L.) son consumidos tradicionalmente en diferentes formas en todo el mundo. Entre los constituyentes de los frutos de noni destacan: iridoides, flavonoides, lignanos, ésteres de ácidos con azúcares, triterpenos y esteroides. Se han reportado un gran número de estudios farmacológicos, in vitro e in vivo, sobre el jugo de noni y sus constituyetes, que muestran un elevado número de posibles efectos beneficiosos, especialmente en tres áreas: cáncer, inflamación y enfermedades metabólicas. A pesar de que en la actualidad se considera que el consumo de jugo de noni es seguro, son necesarios más estudios clínicos que avalen su eficacia y su seguridad (AU)

The leaves and especially the fruits of noni (Morinda citrifolia L.) are traditionally the fruits of noni (Morinda citrifolia L.) are traditionally consumed in different preparations throught the world. The main constituents of noni fruits are: irioids, flavonoids, lignans, fatty acid sugar esters, triterpenes and steroids. A large number of in vitro and in vivo pharmacological studies have been reported on noni fruit juice and its constituents, which show a large number of potential benefits, especially in three areas: cancer, inflammation and metabolic diseases. Although at present it is considered that consumption of noni fruit juice is safe, further clinical studies are needed to support their efficacy and safety (AU)

Antimalarial natural products drug discovery in Panama.

CONTEXT: Malaria is still a major public health problem. The biodiversity of the tropics is extremely rich and represents an invaluable source of novel bioactive molecules. For screening of this diversity more sensitive and economical in vitro methods are needed, Flora of Panama has been studied based on ethnomedical uses for discovering antimalarial compounds. OBJECTIVE: This review aims to provide an overview of in vitro screening methodologies for antimalarial drug discovery and to present results of this effort in Panama during the last quarter century. METHODS: A literature search in SciFinder and PubMed and original publications of Panamanian scientists was performed to gather all the information on antimalarial drug discovery from the Panamanian flora and in vitro screening methods. RESULTS AND CONCLUSIONS: A variety of colorimetric, staining, fluorometric, and mass spectrometry and radioactivity-based methods have been provided. The advantages and limitations of these methods are also discussed. Plants used in ethnomedicine for symptoms of malaria by three native Panamanian groups of Amerindians, Kuna, Ngöbe Buglé and Teribes are provided. Seven most active plants with IC(50) values < 10 µg/mL were identified Talisia nervosa Radlk. (Sapindaceae), Topobea parasitica Aubl.(Melastomataceae), Monochaetum myrtoideum Naudin (Melastomataceae), Bourreria spathulata (Miers) Hemsl.(Boraginaceae), Polygonum acuminatum Kunth (Polygonaceae), Clematis campestris A. St.-Hil. (Ranunculaceae) and Terminalia triflora (Griseb.) Lillo (Combretaceae). Thirty bioactive compounds belonging to a variety of chemical classes such as spermine and isoquinoline alkaloids, glycosylflavones, phenylethanoid glycosides, ecdysteroids, quercetin arabinofuranosides, clerodane-type diterpenoids, sipandinolid, galloylquercetin derivatives, gallates, oleamide and mangiferin derivatives.

A quarter century of pharmacognostic research on Panamanian flora: a review.

Panama is a unique terrestrial bridge of extreme biological importance. It is one of the "hot spots" and occupies the fourth place among the 25 most plant-rich countries in the world, with 13.4 % endemic species. Panamanian plants have been screened for a wide range of biological activities: as cytotoxic, brine shrimp-toxic, antiplasmodial, antimicrobial, antiviral, antioxidant, immunosuppressive, and antihypertensive agents. This review concentrates on ethnopharmacological uses of medicinal plants employed by three Amerindian groups of Panama and on selected plants with novel structures and/or interesting bioactive compounds. During the last quarter century, a total of approximately 390 compounds from 86 plants have been isolated, of which 160 are new to the literature. Most of the work reported here has been the result of many international collaborative efforts with scientists worldwide. From the results presented, it is immediately obvious that the Panamanian flora is still an untapped source of new bioactive compounds.

Identification of oleamide in Guatteria recurvisepala by LC/MS-based Plasmodium falciparum thioredoxin reductase ligand binding method.

Our current research on applications of mass spectrometry to natural product drug discovery against malaria aims to screen plant extracts for new ligands to Plasmodium falciparum thioredoxin reductase (PfTrxR) followed by their identification and structure elucidation. PfTrxR is involved in the antioxidant defense and redox regulation of the parasite and is validated as a promising target for therapeutic intervention against malaria. In the present study, detannified methanol extracts from Guatteria recurvisepala, Licania kallunkiae, and Topobea watsonii were screened for ligands to PfTrxR using ultrafiltration and liquid chromatography/mass spectrometry-based binding experiments. The PfTrxR ligand identified in the extract of Guatteria recurvisepala displayed a relative binding affinity of 3.5-fold when incubated with 1 µM PfTrxR. The ligand corresponding to the protonated molecule m/z 282.2792 [M+ H]+ was eluted at a retention time of 17.95 min in a 20-min gradient of 95% B consisting of (A) 0.1%formic acid in 95% H2O-5% ACN, and (B) 0.1% formic acid in 95% ACN-5% H2O in an LC-QTOF-MS.Tandem MS of the protonated molecule m/z 282.2792 [M + H]+, C18H36NO (DBE: 2; error: 1.13 ppm) resulted in two daughter ions m/z 265.2516[M + H-NH3]+ (DBE: 3; error: 0.35 ppm) and m/z 247.2405 [M + H-NH3-H2O] +, (DBE: 4; error:2.26 ppm). The PfTrxR ligand was identified as oleamide and confirmed by comparison of the retention time, molecular formula, accurate mass,and double bond equivalence with the standard oleamide. This is the first report on the identification of oleamide as a PfTrxR ligand from Guatteria recurvisepala R. E. Fr. and the corresponding in vitro activity against P. falciparum strain K1 (IC50 4.29 µg/mL).

Subcutaneous antifungal screening of Latin American plant extracts against Sporothrix schenckii and Fonsecaea pedrosoi.

CONTEXT: Subcutaneous mycoses are chronic infections caused by slow growing environmental fungi. Latin American plants are used in folk medicine to treat these afflictions. Moreover, the potential of the rich Latin American biodiversity for this purpose has not been fully explored. OBJECTIVES: The aim of the study was to screen Latin American plant extracts against two species of subcutaneous fungi: Sporothrix schenckii and Fonsecaea pedrosoi. MATERIALS AND METHODS: One hundred ninety-five organic extracts from 151 Latin American plants were screened against two subcutaneous fungi by the agar dilution method at a concentration of 100 µg/mL, and minimum inhibitory concentrations (MICs) of active extracts were determined. Positive (amphothericin B) and negative (50% ethanol) controls were used. RESULTS AND DISCUSSION: Twenty eight extracts showed activity at ≤100 µg/mL. Of these, four extracts from Gnaphalium gaudichaudianum DC (Asteraceae), Plumeria rubra L (Apocynaceae), Tecoma stans (L.) Juss. ex Kunth. (Bignoniaceae), and Trichostigma octandum (L.), H. Walter showed activity against F. pedrosoi at MIC 12.5 µg/mL; and, four extracts from Bourreria huanita (Lex.) Hemsl. (Boraginaceae), Phytolacca bogotensis Kunth (Phytolaccaceae), Monnina xalapensis Kunth (Polygalaceae) and Crataegus pubescens (C. Presl) C. Presl (Rosaceae) against S. schenckii. This is the first report on antifungal activity of the Latin American plants against these two subcutaneous fungi. CONCLUSION: S. schenkii and F. pedrosoi were inhibited by B. huanita (MIC: 12.5 and 25 µg/mL), G. gaudichaudianum (MIC: 50 and 12.5 µg/mL) and T. triflora (MIC: 25 µg/mL).

Screening of plants of Amaryllidaceae and related families from Panama as sources of acetylcholinesterase inhibitors.

CONTEXT: This is the first comprehensive study of the acetylcholinesterase (AChE) inhibitory activity of species of the family Amaryllidaceae and 13 related families from Panama. OBJECTIVE: Exploration of the potential sources of AChE inhibitors with radical scavenging activity from Amaryllidaceae and 13 related families from Panama. MATERIALS AND METHODS: The studied plants were screened with anti-acetylcholinesterase bioautographic and DPPH free radical scavenging assays. RESULTS: From the 57 plants studied, eight (14%) showed strong inhibition of AChE, and 29 (51%) plants showed moderate inhibition of AChE. DISCUSSION AND CONCLUSION: Sagittaria lancifolia L. (Alismataceae), Crinum jagus (Thomps.) (Amaryllidaceae), Crinum x amabile Donn (Amaryllidaceae), Crinum zeylanicum (L.) L. (Amaryllidaceae), Crocosmia x crocosmiiflora (Lemoine ex Anonymous) N.E. Br. (Iridaceae), Sisyrinchium tinctorium Kunth (Iridaceae), Agapanthus praecox subsp. orientalis (F.M. Leight.) F.M. Leight. (Liliaceae), and Xyris jupicai Rich. (Xyridaceae) were the most active plants, inhibiting AChE at 100 microg on the TLC bioautographic method for the detection of acetylcholinesterase inhibitors. Out of the eight most active plants, two plants, Crinum zeylanicum (L.) L. and Xyris jupicai Rich., showed antioxidant activity.

Screening of Latin American plants for antiparasitic activities against malaria, Chagas disease, and leishmaniasis.

In order to explore rationally the medical potential of the plant biodiversity of the Central and South American region as a source of novel antiparasitic molecules, a multinational Organization of American States (OAS) project, which included the participation of multidisciplinary research centers from Argentina, Bolivia, Colombia, Costa Rica, Guatemala, Nicaragua and Panama, was carried out during the period 2001-2004. This project aimed at screening organic plant extracts for antitrypanosomal, antileishmanial and antimalarial activities and subsequently isolating and characterizing bioactive molecules. Plants for antiparasitic screening were selected from a database of ethnomedical uses of Latin American plants (PlanMedia) based on the amount of biological and chemical information available in the literature. We report here the evaluation of 452 extracts from 311 plant species in vitro screens against Plasmodium falciparum, Leishmania mexicana, and Trypanosoma cruzi. Out of 311 species tested, 17 plants (5.4%) showed antiparasitic activities at IC(50) values < or = 10 microg/mL. The most active plants were Acnistus arborescens (L.) Schltdl. (Solanaceae) (leaf, EtOH, IC(50): 4 microg/mL) Monochaetum myrtoideum Naudin (Melastomataceae) (leaf, MeOH, IC(50): 5 microg/mL) and Bourreria huanita (Lex.) Hemsl. (Boraginaceae) (branch, EtOH, IC(50): 6 microg/mL). These were selectively active against P. falciparum, L. mexicana and T. cruzi, respectively.

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.

Triterpenes from Warszewiczia coccinea (Rubiaceae) as inhibitors of acetylcholinesterase.

Seventy-six plant extracts from the Panamanian flora have been screened for acetylcholinesterase (AChE) inhibitors by thin-layer chromatography (TLC) bioautography. The most promising extracts with AChE inhibitory and free radical scavenging activities at 100 microg were those of Tabernaemontana panamensis (Markgr., Boiteau & L. Allorge) Leeuwenb., Pentagonia macrophylla Benth., and Warszewiczia coccinea (Vahl) Klotzsch. Bioguided fractionation of W. coccinea stem extract afforded two triterpenes, 3beta,6beta,19alpha-trihydroxy-urs-12-en-28-oic acid (1) and 3beta,6beta-dihydroxy-olean-12-en-28-oic acid (sumaresinolic acid) (2), with AChE inhibitory activity. Their structures were determined by spectroscopic methods. This is the first report of these bioactive triterpenes in W. coccinea.

Composition and biological activity of essential oils from Protium confusum.

The composition and biological activity of the essential oils from leaves, fruits, stems and bark of Protium confusum are reported for the first time. Forty-six to sixty-three constituents were identified ranging from 73.8% to 98.5% of the samples. Limonene (60.2%) was the main component in the fruit oil, whereas spathulenol (19.3%), beta-caryophyllene oxide (14.1%) and beta-caryophyllene (8.0%) reached the highest percentages in the oil from leaves. The volatile oils from bark and stems showed the same major constituents: p-cymen-8-ol (14.4% and 6.1%, respectively), spathulenol (9.5% and 9.0% respectively), and hexadecanoic acid (8.4% and 7.8%, respectively). The composition of the essential oils differed significantly from those of previously investigated Protium species. Three out of the four samples exhibited antibacterial activity against Staphylococcus aureus and Mycobacterium smegmatis, the one from leaves being the most active, with MIC values of 62.5 microg/mL in both cases. No activity against Candida albicans was detected. The bark oil showed the highest larvicidal activity against Aedes aegypti (LC100 = 125 microg/mL).