RESUMEN
Chagas disease and leishmaniasis are among the most widespread neglected tropical diseases, and their current therapies have limited efficacy and several toxic side effects. The present study reports the chemical and antikinetoplastid profiles of extracts from five Salvadoran Celastraceae species against the Trypanosoma cruzi epimastigotes stage and Leishmania amazonensis and Leishmania donovani promastigote forms. The phytochemical profile evinced the presence of flavonoids, tannins, sterols, and triterpenes as the main components in all plant species, whereas quinonemethide triterpenoids (QMTs) were restricted to the root bark of the studied species. Antikinetoplastid evaluation highlights the root bark extracts from Zinowewia integerrima, Maytenus segoviarum, and Quetzalia ilicina as the most promising ones, exhibiting higher potency against T. cruzi (IC50 0.71-1.58 µg/mL) and L. amazonensis (IC50 0.38-2.05 µg/mL) than the reference drugs, benznidazole (IC50 1.81 µg/mL) and miltefosine (IC50 2.64 µg/mL), respectively. This potent activity was connected with an excellent selectivity index on the murine macrophage J774A.1 cell line. These findings reinforce the potential of QMTs as antikinetoplastid agents for the development of innovative phytopharmaceuticals and the plant species under study as a source of these promising lead compounds.
RESUMEN
The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 µM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.
Asunto(s)
Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Physalis/química , Replicación Viral/efectos de los fármacos , Witanólidos/farmacología , Línea Celular , El Salvador , VIH-1/fisiología , Humanos , Estructura Molecular , Componentes Aéreos de las Plantas/químicaRESUMEN
Leishmaniasis and Chagas are among the most significant neglected tropical diseases. Due to several drawbacks with the current chemotherapy, developing new antikinetoplastid drugs has become an urgent issue. In the present work, a bioassay-guided investigation of the root bark of Maytenus chiapensis on Leishmania amazonensis and Trypanosoma cruzi led to the identification of two D:A-friedo-nor-oleanane triterpenoids (celastroloids), 20ß-hydroxy-tingenone (celastroloid 5) and 3-O-methyl-6-oxo-tingenol (celastroloid 8), as promising antikinetoplastid leads. They displayed higher potency on L. amazonensis promastigotes (50% inhibitory concentrations [IC50s], 0.44 and 1.12 µM, respectively), intracellular amastigotes (IC50s, 0.83 and 1.91 µM, respectively), and T. cruzi epimastigote stage (IC50s, 2.61 and 3.41 µM, respectively) than reference drugs miltefosine and benznidazole. This potency was coupled with an excellent selectivity index on murine macrophages. Mechanism of action studies, including mitochondrial membrane potential (Δψm) and ATP-level analysis, revealed that celastroloids could induce apoptotic cell death in L. amazonensis triggered by the mitochondria. In addition, the structure-activity relationship is discussed. These findings strongly underline the potential of celastroloids as lead compounds to develop novel antikinetoplastid drugs.
Asunto(s)
Antiprotozoarios , Leishmania mexicana , Leishmaniasis , Maytenus , Trypanosoma cruzi , Animales , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Leishmaniasis/tratamiento farmacológico , RatonesRESUMEN
A phytochemical investigation of the ethanolic extract of leaves from Piper pseudoarboreum led to the isolation of 3-chlorosintenpyridone 1, an unprecedented chlorinated piperamide, together with the known compounds 2-12. Their structures were established based on 1D and 2D (COSY, ROESY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The proposed biosynthetic pathway of compound 1 is discussed. Compounds 1-12 were tested in vitro for their leishmanicidal potential against promastigote stages of Leishmania amazonensis, L braziliensis, L. guyanensis and L. infantum. Two compounds from this series, the alkamide 1 (IC50 3.4-5.2⯵M) and the fatty acid 9 (IC50 18.7-29.6⯵M) displayed higher or similar potency to Miltefosine, used as the reference drug.
Asunto(s)
Alcaloides/farmacología , Antiprotozoarios/farmacología , Cloro/química , Piper/química , Alcaloides/aislamiento & purificación , Antiprotozoarios/aislamiento & purificación , Leishmania/efectos de los fármacos , Estructura Molecular , Perú , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/químicaRESUMEN
As part of a bioprospecting program aimed at the discovery of undescribed natural products from Salvadoran and Peruvian flora, the phytochemical investigations of four Celastraceae species, Celastrus vulcanicola, Maytenus segoviarum, Maytenus jeslkii, and Maytenus cuzcoina, were performed. The current study reports the isolation and structural characterization of five previously undescribed macrolide sesquiterpene pyridine alkaloids, named vulcanicoline-A, cuzcoinine, vulcanicoline-B, jelskiine, and vulcanicoline-C, along with sixteen known alkaloids. The structures of the alkaloids were established by spectrometric and extensive 1D and 2D NMR spectroscopic analysis, including COSY, HSQC, HMBC, and ROESY experiments. The absolute configurations of alkaloids were proposed based on optical rotation sign, and biogenetic considerations. This study represents the first phytochemical analysis of Maytenus segoviarum.
Asunto(s)
Alcaloides/aislamiento & purificación , Celastraceae/química , Piridinas/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Alcaloides/química , Celastrus , El Salvador , Maytenus/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Perú , Piridinas/química , Sesquiterpenos/químicaRESUMEN
Chemoprevention of human cancer appears to be a feasible strategy for cancer control, especially when chemopreventive intervention is involved during early stages of the carcinogenesis process. As a part of our ongoing research program into new chemopreventive agents, herein are reported the isolation, structural elucidation, and biological evaluation of 10 new (1-10) and three known (11-13) sesquiterpenes with a dihydro-ß-agarofuran skeleton from the leaves of Maytenus jelskii Zahlbr. Their stereostructures have been elucidated by means of spectroscopic analysis, including 1D and 2D NMR techniques, ECD studies, and biogenetic considerations. The isolated metabolites and eight previously reported sesquiterpenes (14-21) were screened for their antitumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Six compounds from this series (4, 5, 11, and 13-15) were found to exhibit higher efficacies than ß-carotene, used as reference inhibitor for EBV-EA activation. In particular, promising antitumor activity was observed for compound 5, exhibiting inhibition even at the lowest concentration assayed (10 mol ratio/TPA). Preliminary structure-activity relationship analysis revealed that the acetate, benzoate, and hydroxy groups are the most desirable substituents on the sesquiterpene scaffold for activity in the EBV-EA activation assay.
Asunto(s)
Anticarcinógenos , Maytenus/química , Sesquiterpenos , Anticarcinógenos/química , Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/farmacología , Antígenos Nucleares del Virus de Epstein-Barr/efectos de los fármacos , Antígenos Nucleares del Virus de Epstein-Barr/farmacología , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Perú , Hojas de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
Three new triterpenoids with an unprecedented 6/6/6/6-fused tetracyclic carbon skeleton, montecrinanesâ A-C (1-3), were isolated from the root bark of Celastrus vulcanicola, along with known D:B-friedobaccharanes (4-6), and lupane-type triterpenes (7-12). The stereostructures of the new metabolites were elucidated based on spectroscopic (1D and 2D NMR) and spectrometric (HR-EIMS and HR-ESIMS) techniques. Their absolute configurations were determined by both NMR spectroscopy, with (R)-(-)-α-methoxyphenylacetic acid as a chiral derivatizing agent, and biogenetic considerations. Biogenetic pathways for montecrinane and D:B-friedobaccharane skeletons were proposed and studied by DFT methods. The theoretical results support the energetic feasibility of the putative biogenetic pathways, in which the 1,2-methyl shift from the secondary baccharenyl cation represents a novel and key reaction step for a new montecrinane skeleton.
Asunto(s)
Celastrus/química , Triterpenos/aislamiento & purificación , El Salvador , Modelos Teóricos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Corteza de la Planta/química , Triterpenos/química , Triterpenos/metabolismoRESUMEN
Quorum sensing (QS), or bacterial cell-to-cell communication, is a key process for bacterial colonization of substrata through biofilm formation, infections, and production of virulence factors. In an ongoing investigation of bioactive secondary metabolites from Piper species, four new flavonoids (1-4), along with five known ones (5-9) were isolated from the leaves of Piper delineatum. Their stereostructures were established by spectroscopic and spectrometric methods, including 1D and 2D NMR experiments, and comparison with data reported in the literature. The compounds were screened for their ability to interfere with QS signaling in the bacterial model Vibrio harveyi. Four compounds from this series (2, 3, 6, and 7) exhibited remarkable activity in the micromolar range, being compounds 3 and 7 particularly attractive since they did not affect bacterial growth. The results suggest that these flavonoids disrupt QS-mediated bioluminescence by interaction with elements downstream LuxO in the QS circuit of V. harveyi, and also, they exhibited a strong dose-dependent inhibition of biofilm formation. The present findings shed light on the QS inhibition mechanisms of flavonoids, underlining their potential applications.
Asunto(s)
Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Piper/química , Percepción de Quorum , Vibrio/fisiología , Biopelículas/efectos de los fármacos , Flavonoides/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Perú , Fenotipo , Piper/microbiología , Hojas de la Planta/química , Vibrio/metabolismoRESUMEN
As a part of our investigation into new anti-HIV agents, we report herein the isolation, structure elucidation, and biological activity of six new (1-6) and 20 known (7-26) pentacyclic lupane-type triterpenoids from the stem of Cassine xylocarpa and root bark of Maytenus cuzcoina. Their stereostructures were elucidated on the basis of spectroscopic and spectrometric methods, including 1D and 2D NMR techniques. To gain a more complete understanding of the structural requirements for anti-HIV activity, derivatives 27-48 were prepared by chemical modification of the main secondary metabolites. Sixteen compounds from this series displayed inhibitory effects of human immunodeficiency virus type 1 replication with IC50 values in the micromolar range, highlighting compounds 12, 38, and 42 (IC50 4.08, 4.18, and 1.70 µM, respectively) as the most promising anti-HIV agents.
Asunto(s)
Fármacos Anti-VIH/aislamiento & purificación , Fármacos Anti-VIH/farmacología , Celastraceae/química , Maytenus/química , Triterpenos/aislamiento & purificación , Triterpenos/farmacología , Fármacos Anti-VIH/química , Antineoplásicos Fitogénicos/química , VIH-1/efectos de los fármacos , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Perú , Corteza de la Planta/química , Tallos de la Planta/química , Relación Estructura-Actividad , Triterpenos/químicaRESUMEN
Multidrug resistance (MDR) caused by the overexpression of ABC drug transporters is a major obstacle in clinical cancer chemotherapy and underlines the urgent need for the development of new, potent, and safe reversal agents. Toward this goal, reported herein are the structure elucidation and biological activity of nine new (1-9) and four known (10-13) dihydro-ß-agarofuran sesquiterpenes, isolated from the leaves of Celastrus vulcanicola, as reversers of MDR mediated by human P-glycoprotein expression. The structures of these compounds were elucidated by extensive NMR spectroscopic and mass spectrometric analysis, and their absolute configurations were determined by circular dichroism studies, chemical correlations (1a, 8a, and 8b), and biogenetic means. Four compounds from this series were discovered as potent chemosensitizers for MDR1-G185 NIH-3T3 murine cells (3, 4, 6, and 7), showing higher efficacies than the classical P-glycoprotein inhibitor verapamil, a first-generation chemosensitizer, when reversing resistance to daunomycin and vinblastine at the lowest concentration tested of 1 µM.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Celastrus/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Transportadoras de Casetes de Unión a ATP/metabolismo , Animales , Dicroismo Circular , Cristalografía por Rayos X , Daunorrubicina/farmacología , Resistencia a Múltiples Medicamentos , El Salvador , Humanos , Ratones , Conformación Molecular , Estructura Molecular , Células 3T3 NIH , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Sesquiterpenos/química , Vinblastina/farmacologíaRESUMEN
Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model.
Asunto(s)
Abietanos/aislamiento & purificación , Abietanos/farmacología , Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/farmacología , Celastraceae/química , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Maytenus/química , Modelos Biológicos , Abietanos/química , Animales , Anticarcinógenos/química , Estudios Cruzados , Diterpenos/química , Antígenos Nucleares del Virus de Epstein-Barr/efectos de los fármacos , Femenino , Ratones , Ratones Endogámicos ICR , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Papiloma/tratamiento farmacológico , Perú , Corteza de la Planta/química , Raíces de Plantas/química , Piel/efectos de los fármacosRESUMEN
Seven new (1-4 and 7-9) sesquiterpenes with a dihydro-beta-agarofuran skeleton, along with four known compounds (5, 6, 10, and 11), have been isolated from the leaves of Maytenus jelskii. The structures of the new compounds were elucidated by means of spectroscopic data analysis, including 1D and 2D NMR techniques, and their absolute configurations were determined by circular dichroism and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compound 10 was found to be an effective antitumor-promoting agent and also showed a potent chemopreventive effect in an in vivo two-stage carcinogenesis model.
Asunto(s)
Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/farmacología , Maytenus/química , Modelos Biológicos , Plantas Medicinales/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Acetilación , Animales , Anticarcinógenos/química , Antígenos Virales/efectos de los fármacos , Femenino , Ratones , Ratones Endogámicos ICR , Conformación Molecular , Estructura Molecular , Perú , Hojas de la Planta/química , Sesquiterpenos/química , Estereoisomerismo , Relación Estructura-Actividad , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
P-Glycoprotein (Pgp) overexpression is one factor contributing to multidrug resistance (MDR) in cancer cells and represents one drawback in the treatment of cancer. In an attempt to find more specific and less toxic anticancer MDR-reversal agents, we report herein the isolation, structure elucidation and biological activity of nine new (, and ) and seven known (, and ) dihydro-beta-agarofuran sesquiterpenes from the leaves of Celastrus vulcanicola. Their stereostructures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, CD studies and biogenetic means. All the compounds were assayed on human MDR1-transfected NIH-3T3 cells, in order to determine their ability to reverse the MDR phenotype due to Pgp overexpression. Six compounds from these series (, , , , and ) showed an effectiveness that was similar to (or higher than) the classical Pgp reversal agent verapamil for the reversal of resistance to daunomycin and vinblastine. The structure-activity relationships are discussed.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Sesquiterpenos/farmacología , Células 3T3 , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/fisiología , Animales , Antineoplásicos , Celastrus/química , Furanos , Humanos , Ratones , Estructura Molecular , Hojas de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/uso terapéutico , Análisis Espectral , Relación Estructura-ActividadRESUMEN
Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively.
Asunto(s)
Antiparasitarios/aislamiento & purificación , Antiparasitarios/farmacología , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Benzoatos/aislamiento & purificación , Benzoatos/farmacología , Piper/química , Plantas Medicinales/química , Animales , Antimaláricos , Antiparasitarios/química , Antiprotozoarios/química , Benzoatos/química , Bolivia , Leishmania/efectos de los fármacos , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Hojas de la Planta/química , Plasmodium falciparum/efectos de los fármacos , Trypanosoma cruzi/efectos de los fármacosRESUMEN
Five new lupane triterpenes (1-5), in addition to 24 known ones, were isolated from Maytenus cuzcoina and M. chiapensis. Their structures were elucidated on the basis of spectroscopic analysis, including homonuclear and heteronuclear correlation NMR (COSY, ROESY, HSQC, and HMBC) experiments. The compounds were assayed for antimicrobial and cytotoxic activities, with 3-epi-betulinic acid and 28,30-dihydroxy-3-oxolup-20(29)-ene showing moderate cytotoxicity.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Bacterias/efectos de los fármacos , Maytenus/química , Triterpenos/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Chlorocebus aethiops , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Triterpenos Pentacíclicos , Perú , Triterpenos/química , Triterpenos/farmacología , Células Tumorales Cultivadas , Ácido BetulínicoRESUMEN
The new sesquiterpene pyridine alkaloids chiapenines ES-I (1), ES-II (2), ES-III (3), and ES-IV (4), in addition to the known alkaloids wilfordine (5), alatamine (6), wilforidine (7), alatusinine (8), euonine (9), euonymine (10), ebenifoline E-I (11), forrestine (12), mayteine (13), and 4-hydroxy-7-epi-chuchuhuanine E-V (14), were isolated from the leaves of Maytenus chiapensis. Their structures were elucidated by 1D and 2D NMR spectroscopy, including homonuclear and heteronuclear correlation (COSY, ROESY, HSQC, and HMBC) experiments. Wilfordine, alatusinine, and euonine exhibited strong antifeedant activity against Spodoptera littoralis.
Asunto(s)
Alcaloides/aislamiento & purificación , Insecticidas/aislamiento & purificación , Maytenus/química , Plantas Medicinales/química , Piridinas/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Alcaloides/química , Alcaloides/farmacología , Animales , Áfidos/efectos de los fármacos , Células Cultivadas , El Salvador , Conducta Alimentaria/efectos de los fármacos , Insecticidas/química , Insecticidas/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Piridinas/química , Piridinas/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Spodoptera/efectos de los fármacosRESUMEN
Two new sesquiterpenoids (1 and 2) with a dihydro-beta-agarofuran skeleton were isolated from Crossopetalum tonduzii. Their structures were elucidated on the basis of spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC). Their absolute configurations were determined by CD studies on 3, the benzoylated derivative of 1. Chemical correlations have allowed the absolute configurations of 4 and 5, two previously known dihydro-beta-agarofuran analogues, to be reported for the first time. Compounds 1, 2, and 5 showed strong antitumor-promoting effects on Epstein-Barr virus early antigen (EBV-EA) activation.
Asunto(s)
Anticarcinógenos/aislamiento & purificación , Antígenos Virales/efectos de los fármacos , Celastraceae/química , Plantas Medicinales/química , Sesquiterpenos/aislamiento & purificación , Acetilación , Anticarcinógenos/química , Anticarcinógenos/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Panamá , Sesquiterpenos/química , Sesquiterpenos/farmacología , EstereoisomerismoRESUMEN
Five new dihydro-beta-agarofuran sesquiterpenes (1-5) were isolated from the leaves of Maytenus chiapensis. The structures of 1-5 were determined by means of 1D and 2D NMR techniques. A semiselective HMBC technique was applied in order to obtain complete (13)C NMR assignments. Absolute configurations were determined by CD studies and chemical correlations and on biogenetic grounds. Compound 4 showed weak activity against a multidrug-resistant Leishmania tropica line.
Asunto(s)
Leishmania tropica/efectos de los fármacos , Maytenus/química , Plantas Medicinales/química , Sesquiterpenos/aislamiento & purificación , Animales , Isótopos de Carbono , Línea Celular/efectos de los fármacos , Dicroismo Circular , Resistencia a Múltiples Medicamentos , El Salvador , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , EstereoisomerismoRESUMEN
Twelve known diterpenes 1 - 11 and 13, and three known sesquiterpenes 14 - 16, along with a new C(20) - C(15) terpenoid 17, with a structure based on an unprecedented skeleton in which a labdane diterpene is linked to a monocyclic sesquiterpene by an ester bridge, were isolated from the oleoresin of the Peruvian medicinal plant Copaifera paupera (Herzog) Dwyer (Leguminosae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlation NMR experiments (COSY, ROESY, HMQC and HMBC), and by comparison with data in the literature. The leishmanicidal, antimicrobial, cytotoxic, and aldose reductase inhibitory activities were studied. Compounds 1 and 11 showed significant antimicrobial activity (MIC < 10 microg/ml) against Gram-positive bacteria, comparable with cephotaxime used as control. Compound 2 exhibited moderate cytotoxic activity against four cancer cell lines.