RESUMEN
Synthesis of 3-deoxy-3a-homo-3a-aza-derivatives of betulin and erythrodiol from betulonic and oleanonic acids was carried out. The most antineoplastic activity with a wide range of action at in vitro testing showed 3-deoxy-3a-homo-3a-aza-28-hydroxy-12(13)-oleanene, which by results of profound studying could be recommended for in vivo investigation. Its modification in the C28 position by introduction of amethoxycinnamoyl fragment led to a loss of antineoplastic activity. 3-Deoxy-3a-homo-3a-aza-derivatives of betulin (3-(aminopropyl)-, 28-(2-carboxyethyl)carboxy-, and 28-cinnamoyloxy-) showed moderate antineoplastic activity in the case of Colon Cancer, Breast Cancer and Leukemia cell lines.
Asunto(s)
Neoplasias/tratamiento farmacológico , Ácido Oleanólico/análogos & derivados , Relación Estructura-Actividad , Triterpenos/síntesis química , Adamantano/síntesis química , Adamantano/química , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Antineoplásicos/química , Antivirales/administración & dosificación , Antivirales/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias/patología , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Triterpenos/químicaRESUMEN
The synthesis and screening of antitumor activity in vitro (cytotoxicity) of various oxygen, nitrogen, sulfur and platinum-containing derivatives of allobetulin, including different arrangements of the double bonds in the A and B rings, penta- and hexacyclic ring A, 21-acetyl-20,28-epoxy-18α,19ßH-ursane-isomeric cycle E, was carry out. (3R,5R)-19ß,28-Epoxy-4,5-seco-18α-olean-3(5)-ozonide and 2,3-indolo-21ß-acetyl-20ß,28-epoxy-18α, H-19ß-ursane showed significant cytotoxic activity against melanoma MeWo and Leukemia SR cells, appropriately. (3S,5S)-Diastereomer of the first compound showed no cytotoxicity.
Asunto(s)
Triterpenos/química , Triterpenos/farmacología , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células Hep G2 , Humanos , Estructura Molecular , Relación Estructura-Actividad , Triterpenos/síntesis químicaRESUMEN
The synthesis of aminopropoxy derivatives of betulin, erythrodiol, uvaol and oleantriol via cyanoethylation of triterpenoids hydroxyl groups and subsequent reduction of cyanoethyl fragments is described. High and specific in vitro antitumor activity (cytotoxicity) of 3beta,28-di-O-[3-(aminopropoxy)]lupa-20(29)-ene and 3beta-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene towards a wide range of human tumor cell lines is discovered. The aminopropoxy group is shown to be a new perspective pharmacophor group for design of anticancer agents on the basis of triterpenoids.
Asunto(s)
Antineoplásicos/síntesis química , Ácido Oleanólico/análogos & derivados , Triterpenos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Ácido Oleanólico/síntesis química , Ácido Oleanólico/química , Ácido Oleanólico/farmacología , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
The synthesis of a new group of triterpenoid acylates on the basis of oleanolic, glycyrrhetic and ursolic acids and betulin is described. In studying the activity of the synthesized compounds in relation to reproduction of virus pathogens of respiratory infections 28-O-methoxycynnamoylbetulin shows high activity against influenza type A (H1N1) the selectivity index SI > 100. The high activity of 3,28-dinicotinoylbetulin against papilloma virus (strain HPV-11) was detected, the selectivity index SI was 35.
Asunto(s)
Antivirales/síntesis química , Subtipo H1N1 del Virus de la Influenza A/fisiología , Papillomaviridae/fisiología , Triterpenos/síntesis química , Antivirales/química , Antivirales/farmacología , Línea Celular , Evaluación de Medicamentos , Humanos , Gripe Humana/dietoterapia , Infecciones por Papillomavirus/tratamiento farmacológico , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
The synthesis of a new group of triterpenoid acylates has been conducted on the basis of oleanolic, glycyrrhetic, and ursolic acids and betulin. 28-ortho-Methoxycynnamoylbetulin has been demonstrated to possess high activity against the influenza type A (H1N1) virus with the selectivity index SI > 100 while studying the activity of the synthesized compounds in relation to the reproduction of viral pathogens of respiratory infections. The high activity of 3,28-dinicotinoylbetulin against the papilloma virus (strain HPV-11) was detected with the selectivity index SI 35.
RESUMEN
Hemisuccinates, hemiphthalates, acetylsalicylates, cinnamates, and p-methoxycinnamates of lupeol, betulin, and 3-O-acetylbetulin were synthesized via interaction with corresponding acid anhydrides or acid chlorides. A number of betulin esters in position 3 and 28 were shown to exhibit a pronounced hepatoprotective effect similar to that of betulin and silibor. These experimental data were in a good agreement with the computer prediction of their biological activity. Betulin 3,28-bis-hemiphthalate was more effective than carsil in models of experimental hepatitis caused by carbon tetrachloride, tetracycline, and ethanol.