RESUMO
The reaction of betulonic acid chloride with 4-amino-2,2,6,6-tetramethylpeperidine-1-oxyl, 3-amino-2,2,5,5-tetramethylpyrrolidine-1-oxyl and 3-aminomethyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl gave corresponding triterpenoid amides. It was found that new derivatives exhibit cytotoxic activity against tumor cells CEM-13, U-937, MT-4. CCID50 value for most activity compound--N-[3-oxolup-20(29)-en-30-yl]-(2,2,6,6-tetramethylpiperidine-4-yl)-1-oxyl--was 5.7-33.1 microM.
Assuntos
Amidas/síntese química , Ácido Oleanólico/análogos & derivados , Terpenos/síntese química , Amidas/química , Amidas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Humanos , Ácido Oleanólico/síntese química , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Marcadores de Spin , Terpenos/química , Terpenos/farmacologiaRESUMO
Betulonic acid amides containing a nitroxyl radical moiety possess antiholestatic effects in mice. Introduction ofpiperidine nitroxide moiety into lupan core increases its hepatoprotective activity. Oral administration of piperidine nitroxide derivative in dose 50 mg/kg doesn't stimulate transplanted tumor growth and raises a lifespan of mice.
Assuntos
Carcinoma Pulmonar de Lewis/tratamento farmacológico , Hepatite/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Piperidinas/administração & dosagem , Pirrolidinas/administração & dosagem , Amidas/administração & dosagem , Amidas/química , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Lewis/patologia , Hepatite/patologia , Humanos , Camundongos , Óxidos de Nitrogênio/química , Ácido Oleanólico/administração & dosagem , Ácido Oleanólico/química , Piperidinas/química , Pirrolidinas/químicaRESUMO
Derivatives of the available plant triterpenes glycyrrhetic acid and betulin (betulin succinates and amides of betulonic and 18beta-glycyrrhetic acids containing fragments of long-chain amino acids and a peptide) were synthesized. The inhibitory action of these compounds on the growth of MT-4, MOLT-4, CEM. and Hep G2 tumor cells and their effect on the apoptosis of these cells were studied. It was shown that betulonic acid amides are more effective inhibitors of the tumor cell growth than the corresponding amides of glycyrrhetic acid. It was also found that betulonic acid amides containing fragments of caprylic, pelargonic, and undecanoic acids are more effective inhibitors of tumor cell growth than betulinic acid. The 17-dipeptide derivative of betulonic acid N-{N-[3-oxo-20(29)-lupen-28-oyl]-9-aminononanoyl}-3-amino-3-phenylpropionic acid exhibited the maximum inhibitory activity toward the tumor cells studied. Data on the induction of apoptosis in tumor cells by betulin derivatives at a concentration of 10 microg/ml were obtained by flow cytometry. The amides of betulonic acid proved to be the most effective inducers of apoptosis.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Glicirretínico/análogos & derivados , Terpenos/química , Triterpenos/química , Antineoplásicos/síntese química , Apoptose , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , PlantasRESUMO
We studied the effects of four synthetic amides of betulonic acid containing amino acid fragments (d,l-alpha-alanine, beta-alanine, and their methyl esters) on the rate of growth and metastatic dissemination of transplantable Lewis lung carcinoma in C57Bl/6 mice. The test compounds were administered intragastrically in a single dose of 500 mg/kg. 3-[-oxo-20(29)-lupen-28-oilamino]-propionic acid suppressed primary tumor growth (by 26%) and decreased the number of lung metastases (by more than 2 times). Antitumor and antimetastatic activity of triterpenoids decreased after methylation of the amino acid fragment in betulonic acid.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Metástase Neoplásica/prevenção & controle , Ácido Oleanólico/análogos & derivados , Alanina/química , Animais , Antineoplásicos/química , Carcinoma Pulmonar de Lewis/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/patologia , Ácido Oleanólico/química , Ácido Oleanólico/uso terapêuticoRESUMO
The purpose of the study was to investigate, in the Vero cell culture, the antiviral activity of vegetable tritrpens derivatives and ribavirin analogues against the viruses of measles, herpes simple (type 1), cytomegaloviruses and filoviruses. The toxicity and antiviral activity of compounds were determined after coloring of cells with crystal violate. Additionally, the combined action of triterpens' derivatives and ribavirin was investigated. The studied compounds showed relatively low antiviral activity, nonetheless, further research of vegetable triterpens and their derivatives as well as ribavirin analogues would be promising.
Assuntos
Antivirais/farmacologia , Citomegalovirus/efeitos dos fármacos , Filoviridae/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Morbillivirus/efeitos dos fármacos , Ribavirina/farmacologia , Triterpenos/farmacologia , Animais , Chlorocebus aethiops , Colorimetria , Citomegalovirus/crescimento & desenvolvimento , Filoviridae/crescimento & desenvolvimento , Herpesvirus Humano 1/crescimento & desenvolvimento , Humanos , Técnicas In Vitro , Pulmão/embriologia , Morbillivirus/crescimento & desenvolvimento , Células VeroAssuntos
Antineoplásicos/efeitos adversos , Hepatite/tratamento farmacológico , Fígado/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Alanina/química , Animais , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Éteres , Fígado/metabolismo , Masculino , Camundongos , Modelos Químicos , Transplante de Neoplasias , Ratos , beta-Alanina/químicaRESUMO
In modeling system of the initiated oxidation of methyl oleate the antioxidation activity of a series of dipeptide derivatives of betulonic and glycyrrhetic acids, natural quinones (ubiquinone, philloquinone and menadione) and the kinetic effects of their combined action with alpha-tocopherol were studied. The same extreme character of the dependence of inhibitory action on the concentration of all investigated substances was found. Combined addition of triterpenoids or quinones together with alpha-tocopherol attenuated their effect. The mechanism of intermolecular interactions of tocopherol with quinones and triterpenoids is offered. The biological importance of these effects is discussed.