RESUMEN
14-O-Cinnamoyl esters of naltrexone (6) were synthesized and evaluated in isolated tissue assays in vitro and in vivo in mouse antinociceptive assays. Their predominant opioid receptor activity was mu receptor (MOR) antagonism, but the unsubstituted cinnamoyl derivative (6a) had partial MOR agonist activity in vitro and in vivo. When compared to the equivalent 14-cinnamoylaminomorphinones (5), the cinnamoyloxy morphinones (6) as MOR antagonists had a shorter duration of action and were less effective as pseudoirreversible antagonists. The antinociceptive activity of the cinnamoyloxycodeinones (7) was not significantly greater than that of the morphinones (6), but they exhibited no evidence of any pseudoirreversible MOR antagonism. In both respects, these profiles differed from those of the equivalent 14-cinnamoylaminocodeinones (4).
Asunto(s)
Hidrocodona/farmacología , Naltrexona/análogos & derivados , Receptores Opioides mu/agonistas , Receptores Opioides mu/antagonistas & inhibidores , Espectroscopía de Resonancia Magnética , Naltrexona/farmacología , Espectrometría de Masa por Ionización de ElectrosprayRESUMEN
A series of diarylamines, diaryl and arylbenzyl ethers based on combretastatin A-4 was prepared and evaluated for anticancer activity. 2-Methoxy-5-(3',4',5'-trimethoxyphenoxymethyl)phenol was the most active (IC50, K562 20 nM) and caused significant G2/M cell cycle arrest.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos/farmacología , Éteres/farmacología , Estilbenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/química , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Colchicina/antagonistas & inhibidores , Colchicina/metabolismo , Éteres/síntesis química , Éteres/química , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Plantas Medicinales/química , Unión Proteica/efectos de los fármacos , Estilbenos/síntesis química , Estilbenos/química , Tubulina (Proteína)/metabolismo , Células Tumorales CultivadasRESUMEN
A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'- trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/toxicidad , Chalcona/análogos & derivados , Chalcona/toxicidad , Antineoplásicos/síntesis química , Ciclo Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Chalcona/síntesis química , Chalcona/química , Cristalografía por Rayos X , Diseño de Fármacos , Humanos , Células K562 , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Relación Estructura-ActividadRESUMEN
A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt base-catalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones of IC(50) less than 1 microM of which 4'-hydroxy-2,4,6,3'-tetramethoxychalcone (5a) was the most active [IC(50) (K562), 30 nM]; it causes cell cycle arrest at the G(2)/M point and binds to tubulin at the colchicine binding site.