RESUMEN
A series of spiro-oxindole derivatives was synthesized by novel regioselective 1,3-dipolar cycloadditions of isatin, α-amino acids, and (E)-ß-aryl-nitro-olefins. Regioisomers were produced in each reaction and the major products showed different regioselectivity compared to previously reported spiro-oxindole derivatives.
Asunto(s)
Química Orgánica/métodos , Indoles/síntesis química , Pirrolidinas/síntesis química , Compuestos de Espiro/síntesis química , Alquenos/química , Aminoácidos/química , Cristalografía por Rayos X , Ciclización , Indoles/química , Isatina/química , Espectroscopía de Resonancia Magnética , Oxindoles , Pirrolidinas/química , Compuestos de Espiro/química , EstereoisomerismoRESUMEN
Six new dibenzo[b,e]oxepinone metabolites, chaetones A-F (1-6), as well as three known compounds, 1-hydroxy-6-methyl-8-hydroxymethylxanthone (7), citreorosein (8), and emodin (9), were obtained from a freshwater-derived fungal strain Chaetomium sp. YMF 1.02105. Their structures were established on the basis of extensive spectroscopic data analysis and comparison with spectroscopic data reported. Compounds 1-6 are further additions to the small group of dibenzo[b,e]oxepinones represented by arugosins A-H. Compounds 1-7 were tested for their cytotoxic activities against A549, Raji, HepG2, MCF-7, and HL-60 cell lines. The results showed that compound 3 had significant cytotoxicity with IC50 values of 1.2, 1.8, 1.9, 2.3, and 1.6 µg/mL, respectively, against the five cancer cell lines. All compounds showed modest antimicrobial activity against Staphylococcus aureus (ATCC 6538) in standard disk assays.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Chaetomium/química , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Antibacterianos/química , Línea Celular Tumoral/efectos de los fármacos , Citotoxinas/química , Dibenzoxepinas/química , Dibenzoxepinas/aislamiento & purificación , Dibenzoxepinas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Agua Dulce/microbiología , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Staphylococcus aureus/efectos de los fármacosRESUMEN
To determine the biosynthesis pathway of the atisine-type diterpenoid alkaloids spiramines A/B and C/D, feeding experiments in in vitro cultured plantlets and enzymatic transformations in cell-free extracts were performed in combination with LCMS and tandem MS analyses. L-[2-(13)C,(15)N]Serine was used in the feeding experiments and enzymatic transformations, and the diterpene spiraminol was identified as a biosynthetic precursor of spiramine alkaloids. The LCMS and tandem MS spectra of the extracts from these experiments indicated that L-[2-(13)C,(15)N]serine was incorporated into spiramines A/B and C/D. The labeled reaction products show that l-serine is the one possible nitrogen source involved in the biosynthesis of atisine-type DAs.
Asunto(s)
Alcaloides/metabolismo , Diterpenos/metabolismo , Medicamentos Herbarios Chinos/metabolismo , Compuestos Heterocíclicos de 4 o más Anillos/metabolismo , Spiraea/química , Alcaloides/química , Diterpenos/química , Medicamentos Herbarios Chinos/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Estructura Molecular , Serina/química , Serina/metabolismoRESUMEN
Three types with six new carboline alkaloids, trigonostemonines A-F (1- 6), were isolated from the roots and stems of Trigonostemon lii. Their structures were elucidated by spectroscopic analyses. It is the first time that beta-carboline alkaloids have been reported in Trigonostemon species. Trigonostemonine F (6) exhibited moderate cytotoxic activity against HL-60 with an IC (50) value of 16 microM.
Asunto(s)
Alcaloides/aislamiento & purificación , Carbolinas/aislamiento & purificación , Euphorbiaceae/química , Alcaloides/química , Carbolinas/química , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Análisis Espectral/métodosRESUMEN
Cipadonoid A ( 1), a novel limonoid with an unprecedented skeleton, was isolated from the leaves of Cipadessa cinerasecns. Its structure and relative configuration were determined by spectroscopic analysis and computer modeling. 1 represents a new type of limonoid, characterized by a rearranged tetrahydropyranyl ring B incorporating usually exocyclic C-30. A possible biosynthetic pathway of 1 was also proposed.
Asunto(s)
Medicamentos Herbarios Chinos/química , Limoninas/química , Meliaceae/química , Plantas Medicinales/química , Dicroismo Circular/métodos , Medicamentos Herbarios Chinos/aislamiento & purificación , Limoninas/aislamiento & purificación , Espectroscopía de Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/normas , Modelos Químicos , Hojas de la Planta/química , Estándares de Referencia , Espectrofotometría Ultravioleta/métodosRESUMEN
Lathyranone A (1), a novel diterpenoid with a rearrangement skeleton, along with a known diterpenoid, Euphorbia factor L(11) (2), was isolated from the seeds of Euphorbia lathyris. The structure and relative stereochemistry of 1 were elucidated by extensive spectroscopic analysis. A possible biosynthetic pathway for lathyranone A (1) was proposed.
Asunto(s)
Diterpenos/química , Euphorbia/química , Vías Biosintéticas , Diterpenos/aislamiento & purificación , Diterpenos/metabolismo , Estructura Molecular , Semillas/química , Análisis Espectral , EstereoisomerismoRESUMEN
Two novel alkaloids, daphlongeranines A (1) and B (2), with an unprecedented ring system, were isolated from the fruits of Daphniphyllum longeracemosum. Their unique structures and relative stereochemistries were established on the basis of spectroscopic and single-crystal diffraction analysis. The proposed biosynthetic pathway was also discussed. Compounds 1 and 2 showed weak inhibition on platelet aggregation.
Asunto(s)
Alcaloides/química , Saxifragaceae/química , Modelos Moleculares , Estructura MolecularRESUMEN
Hostasinine A (1), a benzylphenethylamine alkaloid with an unprecedented skeleton featuring a C-4-C-6 linkage and a nitrone moiety, was isolated from Hosta plantaginea. Its structure was established on the basis of spectroscopic data, and was further confirmed by single-crystal X-ray diffraction. The alkaloid was postulated biogenetically from haemanthidine via N-oxidation and aza-aldol-type condensation and was synthesized biomimetically. The inhibitory activities of 1 on acetylcholinesterase (AChE) and two tumor cell lines (K562 and A549) were also evaluated.
Asunto(s)
Alcaloides/química , Benceno/química , Materiales Biomiméticos/síntesis química , Hosta/química , Fenetilaminas/química , Ácidos/química , Materiales Biomiméticos/química , Estructura Molecular , Fenetilaminas/síntesis químicaRESUMEN
A series of novel thioether pleuromutilin derivatives incorporating various heteroaromatic substituents into the C14 side chain have been reported. Structure-activity relationship (SAR) studies resulted in compounds 52 and 55 with the most potent in vitro antibacterial activity among the series (MIC = 0.031-0.063 µg/mL). Further optimization to overcome the poor water solubility of compound 55 resulted in compounds 87, 91, 109, and 110 possessing good in vitro antibacterial activity with increased hydrophilicity. Compound 114, the water-soluble phosphate prodrug of compound 52, was also prepared and evaluated. Among the derivatives, compound 110 showed moderate pharmacokinetic profiles and good in vivo efficacy in both MSSA and MRSA systemic infection models. Compound 110 was further evaluated in CYP450 inhibition assay and displayed intermediate in vitro inhibition of CYP3A4.
Asunto(s)
Aminopiridinas/síntesis química , Antibacterianos/síntesis química , Diterpenos/síntesis química , Staphylococcus/efectos de los fármacos , Streptococcus/efectos de los fármacos , Sulfuros/síntesis química , Aminopiridinas/farmacocinética , Aminopiridinas/farmacología , Animales , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Citocromo P-450 CYP3A , Inhibidores del Citocromo P-450 CYP3A , Diterpenos/farmacocinética , Diterpenos/farmacología , Diseño de Fármacos , Farmacorresistencia Bacteriana , Estabilidad de Medicamentos , Femenino , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Ratones , Pruebas de Sensibilidad Microbiana , Compuestos Policíclicos , Ratas , Ratas Sprague-Dawley , Solubilidad , Infecciones Estafilocócicas/tratamiento farmacológico , Relación Estructura-Actividad , Sulfuros/farmacocinética , Sulfuros/farmacología , PleuromutilinasRESUMEN
A series of novel benzoxazinyl-oxazolidinones bearing nonaromatic heterocycle or aryl groups were designed and synthesized. Their in vitro and in vivo antibacterial activities were investigated. Most of the (3S, 3aS) biaryl benzoxazinyl-oxazolidinones exhibited potent activity against Gram-positive pathogens. SAR trends were observed; a pyridyl C ring was preferable to other 5- or 6-member aryl C rings, while fluorine substitution on the B ring generated derivatives with reduced activity. Various substituent group positions on the pyridyl ring were also evaluated. The resulting compounds displayed excellent activity against linezolid-resistant strains. Compound 45 exhibited excellent in vitro activity, with a MIC value of 0.25-0.5 µg/mL against MRSA and an activity against linezolid-resistant strains of 8-16-fold higher potency than linezolid. In a MRSA systemic infection model, compound 45 displayed an ED(50) < 5.0 mg/kg, a potency that is nearly 3-fold better than that of linezolid. This compound also showed excellent pharmacokinetic profiles, with a half-life of more than 5 h as well as an oral bioavailability of 81% in rats.
Asunto(s)
Antibacterianos/síntesis química , Benzoxazinas/síntesis química , Oxazolidinonas/síntesis química , Acetamidas/farmacología , Animales , Antibacterianos/química , Antibacterianos/farmacología , Benzoxazinas/química , Benzoxazinas/farmacología , Disponibilidad Biológica , Cristalografía por Rayos X , Diseño de Fármacos , Farmacorresistencia Bacteriana , Femenino , Bacterias Grampositivas/efectos de los fármacos , Linezolid , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Oxazolidinonas/química , Oxazolidinonas/farmacología , Ratas , Ratas Sprague-Dawley , Infecciones Estafilocócicas/tratamiento farmacológico , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
Three unprecedented indole alkaloids, trigonoliimines A-C (1-3) with a unique polycyclic system, were isolated from the leaves of Trigonostemon lii Y. T. Chang. The structures of 1-3 were determined by the spectroscopic, computational, and CD exciton chirality approaches. Trigonoliimine A showed modest anti-HIV-1 activity (EC(50) = 0.95 microg/mL, TI = 7.9).
Asunto(s)
Fármacos Anti-VIH/aislamiento & purificación , Euphorbiaceae/química , Alcaloides Indólicos/aislamiento & purificación , Fármacos Anti-VIH/química , Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacología , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Hojas de la Planta/química , EstereoisomerismoRESUMEN
AIM OF THE STUDY: The rattan stem of Fibraurea recisa Pierre. is known as an ethno-remedy commonly used for the treatment of various skin diseases by the minority Yao, Zhuang and Miao in Yunnan Province of China. The present study was designated to evaluate its antifungal activity, and to root out the antifungal substances from this ethical herb. MATERIALS AND METHODS: The in vitro antifungal assay was performed by agar diffusion test for extracts and fractions. Then, the active fractions were submitted to column chromatography on silica gel and LH-20 to isolate their compounds. And the antifungal activity of pure compounds has been examined by checkerboard microdilution test. Nine Candida strains and one Cryptococcus strain were used for the bioassay. RESULTS: The MeOH extract exhibited significant antifungal activity, and the alkaloidal fractions were deduced as main active component. Subsequent studies led to the identification of a new alkaloid fibrecisine (1) and 21 known alkaloids including berberines, tetrahydroberberines and aporphine derivatives. The bioassay result indicated that the berberines showed more potent activity than aporphine derivatives against the test Candida strains, while tetrahydroberberines showed very weak activity against Cryptococcus neoformans. CONCLUSION: The new alkaloid fibrecisine (1) was identified as 1,2-methylenedioxy-8-hydroxy-6a(R)-aporphine by detailed spectral analysis. The rattan stem of Fibraurea recisa Pierre. is an effective antifungal herb, and its major active component is alkaloidal compounds. Bioassay tests revealed that the water-soluble berberines are the most important antifungal substances. The study provides preliminary scientific validation for the traditional medicinal use of this ethno-remedy.
Asunto(s)
Alcaloides/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Menispermaceae/química , Tallos de la Planta/química , Alcaloides/farmacología , Antifúngicos/farmacología , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría UltravioletaRESUMEN
Five new yuzurimine-type alkaloids, yunnandaphnines A-E (2-6), together with two known analogues, macrodaphniphyllamine (1) and calycinine A (7), have been isolated from the leaves and twigs of Daphniphyllum yunnanense. The structures of the new alkaloids were elucidated by spectroscopic methods. Yunnandaphnine E (6) is a novel heptacyclic yuzurimine-type alkaloid with an oxazine ring.