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1.
J Pharm Sci ; 113(8): 2542-2551, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38815860

RESUMEN

Rotigotine (RTG) is a dopamine agonist used in the treatment of Parkinson's disease. As it is susceptible to oxidation, stability studies must be carefully designed for the identification and characterization of all possible degradation products. Here, RTG degradation was evaluated according to the International Conference on Harmonization guidelines under various stress conditions, including acidic and basic hydrolysis, oxidative, metallic, photolytic, and thermal conditions. Additionally, more severe stress conditions were applied to induce RTG degradation. Significant degradation was only observed under oxidative and photolytic conditions. The samples were analyzed by high performance liquid chromatography coupled to photodiode array detectors, charged aerosol, and high-resolution mass spectrometry. Chromatographic analyses revealed the presence of eight substances related to RTG, four of which were already described and were qualified impurities (impurities B, C, K and E) and four new degradation products (DP-1 - DP-4), whose structures were characterized by high-resolution mass spectrometry through Q-Orbitrap and electrospray ionization. In the stress testing of the active pharmaceutical ingredient in solid form, significant RTG degradation was observed in the presence of the oxidative matrix. The results corroborate the literature that confirm the high susceptibility of RTG to oxidation and the importance of using different detectors to detect degradation products in forced degradation studies.


Asunto(s)
Estabilidad de Medicamentos , Espectrometría de Masa por Ionización de Electrospray , Tetrahidronaftalenos , Tiofenos , Cromatografía Líquida de Alta Presión/métodos , Tiofenos/química , Tiofenos/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Tetrahidronaftalenos/química , Tetrahidronaftalenos/análisis , Oxidación-Reducción , Agonistas de Dopamina/análisis , Agonistas de Dopamina/química , Hidrólisis , Contaminación de Medicamentos/prevención & control , Fotólisis
2.
Org Biomol Chem ; 17(28): 6790-6798, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31241113

RESUMEN

The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.


Asunto(s)
Benceno/química , Ciclooctanos/química , Nitroimidazoles/química , Antineoplásicos/química , Benzoatos/química , Estructura Molecular , Tetrahidronaftalenos/química
3.
An Acad Bras Cienc ; 83(4): 1165-70, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22146952

RESUMEN

Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs along the coast. Chemically it is mainly represented by naphthoquinones, flavonoids, terpenoids and steroids. The aim of the present work is to study quantitative changes in the root metabolic production of Plumbago scandens during different physiologic developmental stages relative to floration. The results indicated the presence of four substances in the extracts: plumbagin, epi-isoshinanolone, palmitic acid and sitosterol, independent on developmental stage. The naphthoquinone plumbagin has always showed to be the major component of all extracts. Naphthoquinones exhibited their highest content during floration, while the content of the two others components decreased during this stage, revealing an inverse profile. The chemical composition changed depending on the plant requirements.


Asunto(s)
Naftoquinonas/química , Ácido Palmítico/química , Raíces de Plantas/química , Plumbaginaceae/química , Sitoesteroles/química , Tetrahidronaftalenos/química , Cromatografía de Gases , Naftoquinonas/metabolismo , Ácido Palmítico/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plumbaginaceae/crecimiento & desarrollo , Plumbaginaceae/metabolismo , Sitoesteroles/metabolismo , Tetrahidronaftalenos/metabolismo
4.
An. acad. bras. ciênc ; 83(4): 1165-1170, Dec. 2011. ilus, tab
Artículo en Inglés | LILACS | ID: lil-607420

RESUMEN

Plumbago scandens L. is a Brazilian tropical/subtropical species that occurs along the coast. Chemically it is mainly represented by naphthoquinones, flavonoids, terpenoids and steroids. The aim of the present work is to study quantitative changes in the root metabolic production of Plumbago scandens during different physiologic developmental stages relative to floration. The results indicated the presence of four substances in the extracts: plumbagin, epi-isoshinanolone, palmitic acid and sitosterol, independent on developmental stage. The naphthoquinone plumbagin has always showed to be the major component of all extracts. Naphthoquinones exhibited their highest content during floration, while the content of the two others components decreased during this stage, revealing an inverse profile. The chemical composition changed depending on the plant requirements.


Plumbago scandens L. é uma espécie brasileira tropical/subtropical que ocorre ao longo da costa. Quimicamente, é principalmente representada por naftoquinonas, flavonóides, terpenóides e esteróides. objetivo do presente trabalho é estudar mudanças quantitativas da produção metabólica nas raízes de Plumbago scandens durante diferentes estágios de desenvolvimento fisiológico, relativos à floração. Os resultados indicaram a presença de quatro substâncias nos extratos: plumbagina, epi-isoshinanolona, ácido palmítico e sitosterol, independente do estágio de desenvolvimento. A naftoquinona plumbagina tem sempre mostrado ser o componente majoritário de todos os extratos. Naftoquinonas exibiram seus maiores conteúdos durante a floração, enquanto o conteúdo dos dois outros componentes decresceu durante este estágio, revelando um perfil inverso. A composição química modificou dependendo das necessidades da planta.


Asunto(s)
Naftoquinonas/química , Ácido Palmítico/química , Raíces de Plantas/química , Plumbaginaceae/química , Sitoesteroles/química , Tetrahidronaftalenos/química , Cromatografía de Gases , Naftoquinonas/metabolismo , Ácido Palmítico/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Plumbaginaceae/crecimiento & desarrollo , Plumbaginaceae/metabolismo , Sitoesteroles/metabolismo , Tetrahidronaftalenos/metabolismo
5.
Acta Crystallogr C ; 65(Pt 2): o35-8, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19190383

RESUMEN

The compound 1,c-3-diphenyltetran-r-1-ol (systematic name: 1,c-3-diphenyl-1,2,3,4-tetrahydro-r-1-naphthol), C(22)H(20)O, which possesses the tetrahydronaphthalene core that is found in a large number of natural products, crystallizes with Z' = 4 and with the four molecules forming a hydrogen-bonded cyclic aggregate. The aliphatic six-membered rings are present with two different conformations in the molecules of the asymmetric unit. A comparison with similar fragments reveals their conformational flexibility. In addition, the structure demonstrates the relative stereochemistries of the chiral centers, which are important since the title compound is used in the stereoselective synthesis of compounds with therapeutic activity.


Asunto(s)
Naftoles/química , Tetrahidronaftalenos/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Modelos Moleculares , Estereoisomerismo , Difracción de Rayos X
6.
7.
Chem Pharm Bull (Tokyo) ; 53(2): 229-31, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15684524

RESUMEN

A new 4alpha-aryltetralin-type lignan called burseranin (1) and a known analogous lignan picropolygamain (2) were isolated along with known triterpenes, lupeol and epi-lupeol from the methanol extract of stems of Bursera graveolens, which showed a remarkable inhibitory activity against human HT1080 fibrosarcoma cells. The whole structure of 1 was established based on combined spectral studies and the absolute structure for 2 was first confirmed by CD spectral evidence. In addition, cytotoxic activities of the stem (methanol) extract and its components are evaluated in this paper.


Asunto(s)
Antineoplásicos Fitogénicos/química , Bursera/química , Lignanos/química , Tetrahidronaftalenos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Dicroismo Circular , Ensayos de Selección de Medicamentos Antitumorales , Humanos , México , Extractos Vegetales/química , Tallos de la Planta/química , Tetrahidronaftalenos/aislamiento & purificación , Tetrahidronaftalenos/farmacología
8.
J Nat Prod ; 66(4): 551-3, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12713414

RESUMEN

HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition has the potential to lead to an anti-retroviral therapy that has advantages over existing therapies. Cytosporic acid (1) is a polyketide-derived novel natural product that was isolated from a fermentation broth of the filamentous fungus Cytospora sp. collected from Puerto Rico. It inhibited strand transfer reaction of HIV-1 integrase with an IC(50) of 20 microM. The isolation, structure elucidation, relative stereochemistry, and activity of 1 are described.


Asunto(s)
Hongos/química , Inhibidores de Integrasa VIH/aislamiento & purificación , VIH-1/enzimología , Tetrahidronaftalenos/aislamiento & purificación , Espectroscopía de Resonancia por Spin del Electrón , Fermentación , Inhibidores de Integrasa VIH/química , Inhibidores de Integrasa VIH/farmacología , Concentración 50 Inhibidora , Estructura Molecular , Puerto Rico , Estereoisomerismo , Tetrahidronaftalenos/química , Tetrahidronaftalenos/farmacología
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