RESUMEN
Twenty-six alkaloids, including the new taberines A-I (1-9), were obtained from Tabernaemontana corymbosa. The structures and absolute configurations were elucidated via MS, NMR, and ECD spectroscopic data analyses. Alkaloids 1-4 are new vobasinyl-ibogan alkaloids, and 1 is characterized by an unusual 1,3-oxazinane moiety. Alkaloids 4 and 16 exhibited moderate cytotoxic potency against various human cancer cell lines, while 4, 10, 11, 13, 14, and 16 showed attenuation of lysosomal acidification activity (EC50: 12.9-29.8 µM), thereby inhibiting autophagic flux.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/farmacología , Tabernaemontana/química , Ácidos , Dicroismo Circular , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Humanos , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura MolecularRESUMEN
Nineteen vobasinyl-ibogan-type bisindole alkaloids, including nine new compounds, taburnaemines A-I (1-9), were isolated from the twigs and leaves of Tabernaemontana corymbosa. The structures and absolute configurations of the new alkaloids were determined by a combination of MS, NMR, and ECD analyses. Alkaloids 1-5 contain a rare 1,3-oxazinane moiety in the vobasinyl unit, while 6 has an uncommon 1,3-oxazolidine moiety in the iboga unit. The absolute configurations of alkaloid 1 and the known alkaloid tabernaecorymbosine A (10) were confirmed by single-crystal X-ray diffraction analysis. All of the bisindole alkaloids, except 2 and 16'-decarbomethoxytabernaecorymbosine A (14), showed antiproliferative activity (IC50 2.6-9.8 µM) against several human cancer cell lines, including A-549, MDA-MB-231, MCF-7, KB, and P-glycoprotein-overexpressing multidrug-resistant KB cells. The preliminary structure-activity relationship correlations are also discussed.
Asunto(s)
Alcaloides Indólicos/química , Tabernaemontana/química , Células A549 , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Alcaloides Indólicos/farmacología , Células KB , Células MCF-7 , Hojas de la Planta/química , Relación Estructura-ActividadRESUMEN
Two new indole alkaloids, winphyllines A (1) and B (4), along with four known alkaloids, Nb-demethylechitamine (2), 17-O-acetylnorechitamine (3), 12-methoxyechitamidine (5), and N(4)-demethylastogustine (6), were isolated from the methanol extract of the twigs of Alstonia rostrata. The structures of 1 and 4 were elucidated by means of HRMS and NMR spectroscopic methods. The in vitro cytotoxic activity of the isolated alkaloids against several human cancer cell lines was evaluated.
Asunto(s)
Alstonia/química , Antineoplásicos Fitogénicos/química , Alcaloides de Triptamina Secologanina/química , Alcaloides de Triptamina Secologanina/farmacología , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Células MCF-7 , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Tabercorymines A (1) and B (2), two new vobasinyl-ibogan-type bisindole alkaloids with an unprecedented skeleton, were isolated from Tabernaemontana corymbosa. Their structures were established by a combination of spectroscopic data, chemical transformation, single-crystal X-ray diffraction, and ECD calculation. Compound 1 represents a novel bisindole alkaloid, characterized by a caged heteropentacyclic ring system incorporating an unprecedented C-7/C-20 bond in the vobasinyl unit. Alkaloids 1 and 2 showed potent antiproliferative activity against several human cancer cell lines, including vincristine-resistant KB.
Asunto(s)
Tabernaemontana , Alcaloides , Antineoplásicos Fitogénicos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura MolecularRESUMEN
Four new Myrioneuron alkaloids, mysumamides A-D (1-4), along with three known ones were isolated from the twigs and leaves of Myrioneuron effusum. All of these alkaloids possessed the tetracyclic skeleton and contained the decahydroquinoline (cis-DHQ) moiety. Their structures and relative configurations were elucidated on the basis of spectroscopic methods, especially 2D NMR techniques. The absolute configuration of 1 was determined by single-crystal X-ray diffraction. The cytotoxic activities of these compounds were also evaluated in vitro.
Asunto(s)
Alcaloides/química , Quinolinas/química , Rubiaceae/química , Alcaloides/aislamiento & purificación , Cristalografía por Rayos X , Estructura Molecular , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Hojas de la Planta/química , Quinolinas/aislamiento & purificaciónRESUMEN
The principal component analysis (PCA) was applied to the data processing in training sets, the new principal components were then used as input data for support vector machine model. A prediction model for optimum pH of chitinase was established based on uniform design. When The regularized constant C, epsilon and Gamma were 10, 0.7 and 0.5 respectively, the calculated pHs fitted the reported optimum pHs of chitinase very well and the MAPEs (Mean Absolute Percent Error) was 3.76%. At the same time, the predicted pHs fitted the reported optimum pHs well and the MAE (Mean Absolute Error) was 0.42 pH unit. It was superior in fittings and predictions compared to the model based on back propagation (BP) neural network.