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
On the basis of betulinic and oleanolic acids triterpenoids with different with different amine fragments: (3-aminopropoxy)-, 3-acetyl-(3-aminopropyl)amino-, 6-[bis(3-aminopropyl)amino]hexylamino-, (3-aminopropyl)-4-aminosulfonyl-4-phenylamino- at positions C3 and C28 were synthesized. It is shown that betulonic acid amide with 4,4'-diaminodiphenylsulfonic substituent don't render antitumor effect in mice with transplantable Lewis lung carcinoma, but possess significant anti-inflammatory activity.
Asunto(s)
Ácido Oleanólico/administración & dosificación , Ácido Oleanólico/síntesis química , Triterpenos/síntesis química , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antineoplásicos/administración & dosificación , Antineoplásicos/síntesis química , Antineoplásicos/química , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/patología , Histamina/toxicidad , Humanos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Ratones , Ácido Oleanólico/química , Triterpenos Pentacíclicos , Triterpenos/química , Ácido BetulínicoRESUMEN
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
Development of the functionalization of triterpenoids to A-secoamidoximes, A-secomethylenamines and branched 3-(3-aminopropylamino)-3-(3-aminopropoxy)amidoximes is illustrated by the betulonic acid ketoxime. An effective way to get of the derivatives of 20,29-dihydrolupanes using diborane is suggested. The antiviral and anti-tuberculosis activity data of some compounds are presented.
Asunto(s)
Antituberculosos/síntesis química , Antivirales/síntesis química , Ácido Oleanólico/análogos & derivados , Oximas/síntesis química , Triterpenos/síntesis química , Antituberculosos/química , Antituberculosos/farmacología , Antivirales/química , Antivirales/farmacología , Humanos , Virus de la Influenza A/efectos de los fármacos , Estructura Molecular , Mycobacterium tuberculosis/efectos de los fármacos , Ácido Oleanólico/química , Oximas/química , Oximas/farmacología , Rhinovirus/efectos de los fármacos , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
N-Methylpiperazinyl amides of betulinic, platanic, glycyrrhetic, oleanolic, ursolic, and moronic acids were synthesized and modified. Betulin and betulonic acid showed antimicrobial activity against Staphylococcus aureus at a concentration of 90 mg/ml, and betulin manifested a bacteriostatic effect against Klebsiella pneumoniae at a concentration of 60 mg/ml. Among the studied N-methylpiperazinyl amides, the highest activity against S. aureus was observed for a betulonic acid derivative.
Asunto(s)
Amidas/síntesis química , Antibacterianos/síntesis química , Piperazinas/síntesis química , Triterpenos/síntesis química , Amidas/química , Amidas/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Recuento de Colonia Microbiana , Klebsiella pneumoniae/efectos de los fármacos , Piperazinas/química , Piperazinas/farmacología , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Triterpenos/química , Triterpenos/farmacologíaRESUMEN
The first derivatives containing two lupan backbones were synthesized by the interaction of betulonic acid chloride with diols (ethylene glycol and diethylene glycol) and monoethanolamine. A modification of ring A of ethylene-l,2-bis(betulonnate) led to its bis(3beta-aminopropyloxy) and bis(3,4-seco-2-cyano) derivatives.