RESUMEN
Separate short and modular syntheses of the isomeric natural products caryolanemagnolol and clovanemagnolol have been achieved starting from commercially available (-)-caryophyllene. The postulated biosynthetic pathways guided the syntheses of the neuroregenerative small molecules allowing their assembly in as few as two steps.
Asunto(s)
Productos Biológicos/síntesis química , Factores de Crecimiento Nervioso/síntesis química , Fenoles/síntesis química , Sesquiterpenos/química , Sesquiterpenos/síntesis química , Productos Biológicos/biosíntesis , Productos Biológicos/química , Biomimética , Conformación Molecular , Factores de Crecimiento Nervioso/biosíntesis , Factores de Crecimiento Nervioso/química , Fenoles/química , Sesquiterpenos Policíclicos , EstereoisomerismoRESUMEN
We recently identified bis(amide) CCG-1423 (1) as a novel inhibitor of RhoA/C-mediated gene transcription that is capable of inhibiting invasion of PC-3 prostate cancer cells in a Matrigel model of metastasis. An initial structure-activity relationship study focusing on bioisosteric replacement of the amides and conformational restriction identified two compounds, 4g and 8, with improved selectivity for inhibition of RhoA/C-mediated gene transcription and attenuated cytotoxicity relative to 1. Both compounds were also capable of inhibiting cell invasion with equal efficacy to 1 but with less attendant cytotoxicity.