RESUMEN
Eight cephalotaxine-type alkaloids (1-8), including two new compounds cephafortunines A and B (1-2), were isolated from the branches and leaves of Cephalotaxus fortunei var. alpina. Their structures were identified by a series of spectroscopic methods (MS, UV, IR, 1D, and 2D NMR) and comparison with the reported data of known analogs. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations. 1-8 were evaluated for their in vitro antiproliferation effects against two human leukemia cell lines (U937 and HL-60). All compounds showed different levels of antiproliferation effects against U937 cells with GI50 values of 4.21-23.70 µM. 4 and 5 were the most active against U937 cells with GI50 values of 4.21 and 6.58 µM and against HL-60 cells with GI50 values of 6.66 and 6.70 µM, respectively. 4 and 5 arrested HL-60 cell cycle in G0/G1 phase.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Cephalotaxus/química , Harringtoninas/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , China , Células HL-60 , Harringtoninas/aislamiento & purificación , Humanos , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Hojas de la Planta/química , Células U937RESUMEN
Two nonbiaryl axially chiral ß-carboline-quinazoline dimers, pegaharmols A (1) and B (2), were isolated from the roots of Peganum harmala. Their planar structures were elucidated by the spectroscopic methods of high-resolution mass spectrometry and 1D and 2D nuclear magnetic resonance (NMR). The stereochemistry was established by a comparison between the experimental data of NMR and electronic circular dichroism and the computed data by quantum mechanical calculations. It is discovered for the first time that the ß-carboline at the C-8 position is bonded to the vasicine at the C-9 position. 1 exhibited moderate cytotoxic activity against HL-60 and A549 cell lines.
Asunto(s)
Alcaloides/química , Antineoplásicos Fitogénicos/farmacología , Carbolinas/farmacología , Peganum/química , Raíces de Plantas/química , Quinazolinas/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Carbolinas/química , Carbolinas/aislamiento & purificación , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Estructura Molecular , Extractos Vegetales/químicaRESUMEN
Inspired by the intriguing structures and bioactivities of dimeric alkaloids, 11 new thalifaberine-type aporphine-benzylisoquinoline alkaloids, thalicultratines A-K, a tetrahydroprotoberberine-aporphine alkaloid, thalicultratine L, and five known ones were isolated from the roots of Thalictrum cultratum. Their structures were defined on the basis of NMR and HRESIMS data. The antiproliferative activities of compounds 1-17 were evaluated against human leukemia HL-60 and prostate cancer PC-3 cells. Most alkaloids showed potent cytotoxicity against selected cancer cells. Preliminary SARs are discussed. The most active new compound (3), with an IC50 value of 1.06 µM against HL-60 cells, was selected for mechanism of action studies. The results revealed that compound 3 induced apoptosis and arrested the HL-60 cell cycle at the S phase with the loss of mitochondria membrane potential. The nuclear morphological Hoechst 33258 staining assay was also carried out, and the results confirmed apoptosis.
Asunto(s)
Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Aporfinas/aislamiento & purificación , Aporfinas/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Raíces de Plantas/química , Thalictrum/química , Alcaloides/química , Antineoplásicos Fitogénicos/química , Aporfinas/química , Alcaloides de Berberina , Medicamentos Herbarios Chinos/química , Células HL-60 , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Relación Estructura-ActividadRESUMEN
Investigation of the alkaloids from Peganum harmala seeds yielded two pairs of unique racemic pyrroloindole alkaloids, (±)-peganines A-B (1-2); two rare thiazole derivatives, peganumals A-B (3-4); six new ß-carboline alkaloids, pegaharmines F-K (5-10); and 12 known analogues. Their structures, including stereochemistry, were elucidated through spectroscopic analyses, quantum chemistry calculations, and single-crystal X-ray diffraction. Notably, the incorporation of pyrrole and indole moieties in peganines A-B, thiazole fragments in peganumals A-B, and a C-1 α,ß-unsaturated ester motif in pegaharmine F (5) are all rare, and their presence in the genus Peganum were demonstrated for the first time. All isolates were tested for antiproliferative activities against the HL-60, PC-3, and SGC-7901 cancer cell lines, and compounds 9, 11, 12, and 13 exhibited moderate cytotoxicity against HL-60 cancer cell lines with IC50 values in the range of 4.36-9.25 µM.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Alcaloides Indólicos/química , Alcaloides Indólicos/aislamiento & purificación , Peganum/química , Semillas/química , Antineoplásicos Fitogénicos/farmacología , Carbolinas/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/farmacología , Células HL-60 , Humanos , Alcaloides Indólicos/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by (1)H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, (1)H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized ß-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using ß-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.
Asunto(s)
Antineoplásicos Fitogénicos/química , Carbolinas/química , Oligodesoxirribonucleótidos/química , Peganum/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Secuencia de Bases , Vías Biosintéticas , Carbolinas/aislamiento & purificación , Carbolinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , G-Cuádruplex , Células HL-60 , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Peganum/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Semillas/químicaRESUMEN
Four quinolone alkaloids (1-4) and three indole alkaloids (20-22), together with 30 known alkaloids (5-19, 23-37), were isolated from the fruits of Euodia rutaecarpa. Their structures were established by spectroscopic analyses. The in vitro cytotoxic activities of these alkaloids against leukaemia HL-60 and prostate cancer PC-3 cell lines were evaluated.
Asunto(s)
Antineoplásicos Fitogénicos/química , Evodia/química , Alcaloides Indólicos/química , Quinolonas/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Frutas/química , Células HL-60 , Humanos , Alcaloides Indólicos/aislamiento & purificación , Masculino , Estructura Molecular , Extractos Vegetales/química , Neoplasias de la Próstata/patología , Quinolonas/aislamiento & purificaciónRESUMEN
Two new 7,6'-coupled naphthylisoquinolines, namely ancistrotectorines A (1) and B (2), two new 5,3'-coupled naphthylisoquinolines, namely ancistrotectorines C (3) and D (4), and one new 7,8-coupled naphthylisoquinoline, namely ancistrotectorine E (5), together with 9 known naphthylisoquinoline alkaloids, hamatine (6), ancistrobertsonine B (7), ancistrocladinine (8), hamatinine (9), ancistrotanzanine A (10), ancistrotanzanine B (11), ancistrotectoriline B (12), 7-epi-ancistrobrevine D (13), and ancistrotectorine (14), were isolated from the 70% EtOH extract of Ancistrocladus tectorius. Their structures were elucidated based on the extensive analysis of spectroscopic data (1D, 2D NMR and MS). Compound 5 exhibited inhibitory activities against HL-60, K562 and U937 cell lines with IC50 values of 1.70, 4.18 and 2.56 µM respectively.
Asunto(s)
Isoquinolinas/aislamiento & purificación , Leucemia/tratamiento farmacológico , Magnoliopsida/química , Naftoles/uso terapéutico , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Células HL-60 , Humanos , Concentración 50 Inhibidora , Isoquinolinas/química , Isoquinolinas/farmacología , Células K562 , Estructura Molecular , Naftoles/química , Naftoles/aislamiento & purificación , Naftoles/farmacología , Fitoterapia , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta/química , Tallos de la Planta/química , Células U937RESUMEN
Six new triterpene saponins, clematomandshurica saponins F-K (1-6), together with a known compound (7), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis. Compounds 5-7 exhibited antiproliferative effects against PC-3 human prostate cancer cells with GI50 values of 1.29, 1.50, and 0.71 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Clematis/química , Saponinas/farmacología , Triterpenos/farmacología , Antineoplásicos Fitogénicos/química , Isótopos de Carbono/análisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular , China , Humanos , Hidrólisis , Espectroscopía de Resonancia Magnética , Medicina Tradicional China , Estructura Molecular , Raíces de Plantas/química , Plantas Medicinales , Rizoma/química , Saponinas/química , Saponinas/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Five new 3,4-seco-lanostane-type triterpenoids, seco-coccinic acids G-K (1-5), and a known compound, seco-coccinic F, were isolated from the roots of Kadsura coccinea (Lem.) A.âC. Sm. Their structures were elucidated by spectroscopic methods, including 2D-NMR and HR-MS techniques. The cell growth inhibitory effects of these compounds were assayed in human leukemia HL-60 cells, and it was found that 1, 5, and 6 showed antiproliferative effects with GI50 values of 28.4, 15.2, and 16.6 µM, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Kadsura/química , Lanosterol/farmacología , Triterpenos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Células HL-60 , Humanos , Lanosterol/química , Lanosterol/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Raíces de Plantas/química , Plantas Medicinales , Espectrometría de Masa por Ionización de Electrospray , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
Three new phenolic compounds, thamnoliadepsides A (1), B (2), and thamnolic acid A (3), and seven known compounds, everninic acid (4), baeomycesic acid (5), ß-orcinol (6), ß-resorcylic acid (7), ethyl orsellinate (8), squamatic acid (9), and vermicularin (10), were isolated from the lichen Thamnolia vermicularis (Sw.) Ach. ex Schaerer. Their structures were determined based on spectroscopic analysis, including 2D-NMR experiments and HR-MS techniques. Compound 1 inhibited growth of prostate cancer cells and bonded to G-quadruplex DNA based on NMR determination.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Líquenes/química , Fenoles/aislamiento & purificación , Fenoles/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Benzoatos/química , Benzoatos/aislamiento & purificación , Benzoatos/farmacología , Línea Celular Tumoral/efectos de los fármacos , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/aislamiento & purificación , Hidroxibenzoatos/farmacología , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas/métodos , Conformación Molecular , Fenoles/química , Neoplasias de la Próstata/patología , Resorcinoles/química , Resorcinoles/aislamiento & purificación , Resorcinoles/farmacologíaRESUMEN
Two new triterpenoids, 3-oxotirucalla-7,9(11),24-trien-21-oic acid (1) and 18Hα,3ß,20ß-ursanediol (2), along with 15 known triterpenes, α-amyrin, α-boswellic acid, ß-boswellic acid, acetyl α-boswellic acid, acetyl ß-boswellic acid, 9,11-dehydro-ß-boswellic acid, 9,11-dehydro-α-boswellic acid, acetyl 11α-methoxy-ß-boswellic acid, 11-keto-ß-boswellic acid, acetyl 11-keto-ß-boswellic acid, acetyl α-elemolic acid, 3ß-hydroxytirucalla-8,24-dien-21-oic acid, elemonic acid, 3α-hydroxytirucalla-7,24-dien-21-oic acid, and 3α-hydroxytirucall-24-en-21-oic acid, were isolated from the resin of Boswellia carterii Birdw.
Asunto(s)
Boswellia/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Triterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/química , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Resinas de Plantas/química , Estereoisomerismo , Triterpenos/químicaRESUMEN
A new friedelane-type triterpene (1), along with seven known triterpenoids, was isolated from the stems and leaves of Calophyllum inophyllum Linn. Their structures were established as 3beta, 23-epoxy-friedelan-28-oic acid (1), friedelin (2), epifriedelanol (3), canophyllal (4), canophyllol (5), canophyllic acid (6), 3-oxo-friedelan-28-oic acid (7), and oleanolic acid (8) by spectroscopic methods (NMR, EI-MS). The growth inhibitory effects of these triterpenoids on human leukemia HL-60 cells were determined.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Calophyllum/química , Triterpenos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Estructura Molecular , Triterpenos/químicaRESUMEN
Two new triterpenoids, 2alpha-hydroxy-3beta-O-acetyllup-20(29)-en-28-oic acid (1) and 3- O-(4'- O-acetyl)-alpha- L-arabinopyranosyloleanolic acid ( 2), together with two known triterpenoids, betulinic acid ( 3) and messagenic acid ( 4) were isolated from the CHCl3 extract of Garcinia hanburyi resin. The structures were elucidated by analysis of the NMR spectroscopic data. The antiproliferative effects and the apoptosis induction abilities of compounds 1 and 2 were determined in four human leukemia cell lines. Compound 2 was more potent than compound 1 in inhibiting cell growth with IC50 values of 2.45, 2.69, 2.42, and 4.15 microM in HL-60, NB4, U937 and K562 cells, respectively.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Garcinia/química , Resinas de Plantas/química , Triterpenos/química , Triterpenos/farmacología , Línea Celular Tumoral , Humanos , Concentración 50 Inhibidora , Leucemia , Estructura MolecularRESUMEN
Three new sterols, 3beta,16alpha-dihydroxy-5alpha,17beta-cholestan-21-carboxylic acid (1), 3beta-acetoxy-16alpha-hydroxy-5alpha,17beta-cholestan-21-carboxylic acid (2) and 3beta-(3-hydroxybutyroxy)-16alpha-hydroxy-5alpha,17beta-cholestan-21-carboxylic acid (3) were isolated from Selaginella tamariscina (Beauv.) Spring (Selaginellaceae). Their structures were elucidated based on NMR analyses. The growth inhibitory effects and differentiation induction abilities of compounds 1 - 3 were determined in human leukemia HL-60 cells. Compound 1 was more effective than compounds 2 and 3 in inhibiting cell growth, but compound 3 was more effective than compounds 1 and 2 in enhancing induction of all- trans-retinoic acid differentiation.