Synthesis and in vitro cytotoxic evaluation of novel 3,4,5-trimethoxyphenyl substituted β-carboline derivatives

To elucidate further our SARs' study on the chemistry and cytotoxic activity and probe the structural requirement for the potent antitumor activity of β-carbolines, a series of novel 1,9-disubstituted and 1,3,9-trisubstituted β-carboline derivatives were designed and synthesized from the starting material l-tryptophan and 3,4,5-trimethoxybenezaldehyde. Cytotoxic activities of these compounds in vitro were investigated, and the SARs associated with position-1, 3 and 9 substituents in β-carbolines have also been discussed. It has been observed that these compounds only displayed moderate to weak cytotoxic activities. Interestingly, most of the investigated compounds displayed selectively cytotoxic activities to human BCG-823 cell lines with IC50 value lower than 100 μM. In addition, the short alkyl substituents in position-9 increased the cytotoxic activities with the tendency of n-butyl > ethyl > methyl. These data confirmed that (1) an alkyl substituent at position-9 of β-carboline nucleus plays an important role in determining their antitumor activities; (2) different β-carbolines bearing various substituents in β-carboline nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects.

A series of novel 3,4,5-trimethoxyphenyl substituted β-carboline derivatives were designed and synthesized from the starting material l-tryptophan and 3,4,5-trimethoxybenezaldehyde. Cytotoxic activities of these compounds in vitro were investigated. Most of the investigated compounds displayed selectively cytotoxic activities to human BCG-823 cell lines.Figure optionsDownload as PowerPoint slide