RESUMO
Plants of the Amaryllidaceae family are well-known (not only) for their ornamental value but also for the alkaloids that they produce. In this report, the first phytochemical study of Clinanthus genus was carried out. The chemical composition of alkaloid fractions from Clinanthus microstephium was analyzed by GC/MS and NMR. Seven known compounds belonging to three structural types of Amaryllidaceae alkaloids were identified. An epimeric mixture of a haemanthamine-type compound (6-hydroxymaritidine) was tested as an inhibitor against acetyl- and butyrylcholinesterase enzymes (AChE and BChE, respectively), two enzymes relevant in the treatment of Alzheimer's disease, with good results. Structure-activity relationships through molecular docking studies with this alkaloid and other structurally related compounds were discussed.
Assuntos
Alcaloides/química , Alcaloides de Amaryllidaceae/química , Amaryllidaceae/química , Inibidores da Colinesterase/química , Fenantridinas/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Alcaloides/metabolismo , Alcaloides/farmacologia , Amaryllidaceae/metabolismo , Sítios de Ligação , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Domínio Catalítico , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Relação Estrutura-AtividadeRESUMO
Nine withanolides were isolated from the aerial parts of Deprea bitteriana, Depreacuyacensis, and Depreazamorae. D.bitteriana yielded two withaphysalins, D. cuyacensis gave two 13,14-seco withaphysalins, while D. zamorae yielded five physangulidines. The compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). All compounds isolated from D.bitteriana and D. cuyacensis were obtained as epimeric mixtures at C-18. The structure of physangulidine D was confirmed by X-ray diffraction analysis. The skeletons found in this research support the chemotaxonomical position of the genus Deprea in the tribe Physalideae.
Assuntos
Solanaceae/química , Vitanolídeos/isolamento & purificação , Colômbia , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Componentes Aéreos da Planta/química , Solanaceae/classificação , Solanaceae/genética , Vitanolídeos/químicaRESUMO
Nine new ß-dihydroagarofurans (1-9) and four new sesquiterpene pyridine alkaloids (10-13) were isolated from the leaves of Maytenus spinosa. Their structures were determined mainly by 1D- and 2D-NMR spectroscopic studies. The absolute configuration of compound 6 was established using CD spectroscopy. Several derivatives (14-20) were prepared from the sesquiterpene 13. Most of the sesquiterpenoids were tested for anti-HIV activity, but only compound 1 was found to be active.
Assuntos
Alcaloides/isolamento & purificação , Fármacos Anti-HIV/isolamento & purificação , Maytenus/química , Plantas Medicinais/química , Piridinas/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Alcaloides/química , Alcaloides/farmacologia , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Argentina , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Piridinas/química , Piridinas/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Two new and five known withanolides (jaborosalactones 2, 3, 4, 5, and 24) were isolated from the leaves of Jaborosa runcinata Lam. We also obtained some derivatives from jaborosalactone 5, which resulted to be the major isolated metabolite. The natural compounds as well as derivatives were evaluated for their antiproliferative activity and the induction of quinone reductase 1 (QR1; NQ01) activity. Structure-activity relationships revealed valuable information on the pharmacophore of withanolide-type compounds. Three compounds of this series showed significantly higher antiproliferative activity than jaborosalactone 5. The effect of these compounds on the cell cycle was determined. Furthermore, the ability of major compounds to induce QR1 was evaluated. It was found that all the active test compounds are monofunctional inducers that interact with Keap1. The most promising derivatives prepared from jaborosalactone 5 include (23R)-4ß,12ß,21-trihydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-26,23-olide (18) and (23R)-21-acetoxy-12ß-hydroxy-1,22-dioxo-12,23-cycloergostan-2,5,17,24-tetraen-26,23-lactame (20).
Assuntos
Antineoplásicos/farmacologia , Quinona Redutases/metabolismo , Vitanolídeos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Conformação Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Vitanolídeos/química , Vitanolídeos/metabolismoRESUMO
Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , Triterpenos/síntese química , Triterpenos/farmacologia , Fármacos Anti-HIV/química , Dicroísmo Circular , Cristalografia por Raios X , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Triterpenos/químicaRESUMO
Three withanolides were isolated from the aerial parts of Jaborosa reflexa Phil. Jaborosa cabrerae Barboza yielded five sativolide withanolides (including jaborosalactones R, S, 38, and 39) and two trechonolide withanolides epimeric at C-23 (trechonolide A and jaborosalactone 32). In addition, five derivatives were obtained by chemical derivatization of jaborosalactone 38, and all compounds were fully characterized by 1D and 2D NMR spectroscopic studies. The in vitro antiproliferative activities of the major natural withanolides and the semisynthetic derivatives were examined against HBL-100, HeLa, SW1573, T-47D, and WiDr human solid tumor cancer cell lines. Some chemotaxonomic considerations are discussed.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Solanaceae/química , Vitanolídeos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Biomarcadores/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Componentes Aéreos da Planta/química , Solanaceae/classificação , Relação Estrutura-Atividade , Vitanolídeos/química , Vitanolídeos/isolamento & purificaçãoRESUMO
Four new dihydroagarofurans (1-4) were isolated from the root bark of Plenckia integerrima. The structures of 1-4 were determined by means of 1D and 2D NMR techniques, and circular dichroism (CD) was used to determine the absolute configuration of compound 1.
Assuntos
Fármacos Anti-HIV/química , Celastraceae/química , Extratos Vegetais/química , Sesquiterpenos/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Sobrevivência Celular , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Casca de Planta/química , Raízes de Plantas/química , Plantas Medicinais/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , EstereoisomerismoRESUMO
The in vitro antiproliferative activity of a series of 22 naturally occurring withanolides was examined against the T-47D, MCF7, MCF7/BUS, MDA-MB-231, and SK-Br-3 human solid tumor breast cancer cell lines. The most active compound showed GI(50) values in the range 0.16-0.71 muM. The aromatic withanolide 19 exhibited specific activity for the estrogen-receptor-positive cell lines (T-47D, MCF7, and MCF7/BUS). Overall, the results demonstrated the relevance of the substitution pattern on the A and B rings on the resultant antiproliferative activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/patologia , Vitanolídeos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Técnicas de Química Combinatória , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-Atividade , Vitanolídeos/químicaRESUMO
Four new alkaloids (1-4) have been isolated from a methanolic extract of bulbs of Pancratium canariense, together with 12 known alkaloids (5-16). The structures of the new alkaloids were determined by extensive 1D and 2D NMR spectroscopic studies and X-ray diffraction.
Assuntos
Alcaloides de Amaryllidaceae/química , Alcaloides de Amaryllidaceae/isolamento & purificação , Liliaceae/química , Plantas Medicinais/química , Cristalografia por Raios X , Conformação Molecular , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EspanhaRESUMO
Six new trechonolide type withanolides (compounds 1- 6), together with trechonolide A, jaborotetrol, and 12- O-methyl jaborosotetrol, were isolated from the aerial parts of Jaborosa laciniata. The structures were elucidated on the basis of spectroscopic methods (1D and 2D NMR, MS).
Assuntos
Plantas Medicinais/química , Solanaceae/química , Vitanolídeos/química , Vitanolídeos/isolamento & purificação , Argentina , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
Seven new withanolides (1-7) were isolated from the aerial parts of Jaborosa caulescens var. caulescens and Jaborosa caulescens var. bipinnatifida. Three of the new compounds are related to jaborosalactones R, S, and T with a delta-lactone side chain and a hemiketal (or ketal) ring formed between a 21-hydroxyl and a 12-ketone (1-3). Compounds 4-7 are trechonolide-type withanolides with a gamma-lactone side chain and a hemiketal (or ketal) ring formed between a 22-hydroxyl and a 12-ketone. Compounds 4 and 5 also contain a hydroxyl group at C-21. Compounds 1, 2, and 7 showed selective phytotoxicity toward monocotyledonous and dicotyledonous species.
Assuntos
Ergosterol , Herbicidas , Plantas Medicinais/química , Solanaceae/química , Argentina , Avena/efeitos dos fármacos , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Germinação/efeitos dos fármacos , Herbicidas/química , Herbicidas/isolamento & purificação , Herbicidas/farmacologia , Lactuca/efeitos dos fármacos , Estrutura Molecular , Plântula/efeitos dos fármacosRESUMO
Twelve new withanolides were isolated from the aerial part of Jaborosa rotacea: five had a spiranoid delta-lactone (1-5); one contained a 26,12-delta-lactone and a C-12-C-23 bond (6); five corresponded to trechonolide-type withanolides with configuration at C-23 opposite of those previously isolated (7, 8, 10-12); two of these have an additional oxido-bridge between C-21 and C-24; finally a withanolide with a hemiketal ring formed between a 21-hydroxyl and a 12-ketone (13) and the closely related jaborosalactone R were also isolated. New compounds were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS). The structures of the spiranoid withanolide and of the epimer of trechonolide A were confirmed by X-ray diffraction studies. Compounds 4, 5, 6, and 8 showed selective phytotoxicity toward monocotyledoneous and dicotyledoneous species.
Assuntos
Ergosterol , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Solanaceae/química , Argentina , Cristalografia por Raios X , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Conformação Molecular , Estrutura Molecular , Phalaris/efeitos dos fármacos , Phalaris/crescimento & desenvolvimentoRESUMO
Six new withanolides (1-6) were isolated from the aerial parts of Jaborosa bergii plants and characterized by spectroscopic methods (1D and 2D NMR, MS). Five of the new compounds presented a novel norbornane-type structure in ring D of the steroid nucleus (1-5), resulting from a carbon-carbon bond between C-15 and C-21. The sixth withanolide isolated was the 5alpha-chloro-6beta-hydroxy analogue (6) of 2,3-dehydrojaborosalactol M (7), previously isolated from this plant. Compound 1 showed selective phytotoxicity toward monocotiledoneous and dicotiledoneous species.
Assuntos
Ergosterol , Plantas Medicinais/química , Solanaceae/química , Argentina , Relação Dose-Resposta a Droga , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/isolamento & purificação , Ergosterol/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , EstereoisomerismoRESUMO
Six new spiranoid withanolides, (20R,22R,23S)-5alpha-chloro-6beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (2), (20R,22R,23S)-5beta,6beta-epoxy-12beta,17beta,22-trihydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (3), (20R,22R,23S)-5beta,6beta-epoxy-4beta,12beta,17beta,22-tetrahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (4), (20R,22R,23S)-5alpha,6beta,12beta,17beta,22-pentahydroxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (5), (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-5alpha-methoxy-1-oxo-12,23-cycloergosta-2,24-dien-26,23-olide (6), and (20R,22R,23S)-6beta,12beta,17beta,22-tetrahydroxy-2alpha,5alpha-epidioxy-1-oxo-12,23-cycloergosta-3,24-dien-26,23-olide (7), were isolated from the leaves of Jaborosa odonelliana. Compounds 2-7 were characterized by a combination of spectroscopic methods (1D and 2D NMR, MS) and molecular modeling.
Assuntos
Lactonas/isolamento & purificação , Plantas Medicinais/química , Solanaceae/química , Animais , Argentina , Carcinoma Hepatocelular , Cromatografia Líquida , Ensaios de Seleção de Medicamentos Antitumorais , Comportamento Alimentar/efeitos dos fármacos , Lactonas/química , Lactonas/farmacologia , Espectrometria de Massas , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Folhas de Planta/química , Estereoisomerismo , Tribolium/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.