Synthesis and cytotoxicity of (R)‐ and (S)‐ricinoleic acid amides and their acetates

Abstract

An environment-friendly, free of solvent, process for the synthesis of (R)- and (S)-ricinoleic acid amides has been developed. Starting from methyl ricinoleates and pyrrolidine or ethanolamine, the corresponding amides were obtained with yields ranging from 83-88%. Among 12 synthesized derivatives of ricinoleic acid, including the starting methyl esters, amides, and their acetates, nine compounds were obtained and tested for the first time. Studies on ricinoleic acid derivatives cytotoxicity showed that methyl esters were the least cytotoxic compounds and modification of their structure resulted in increasing cytotoxicity of the obtained products against both cancer cells and normal lymphocytes. Both enantiomers of the ethanolamine-derived amides showed the most promising anticancer potential.

Cytotoxic and genotoxic effects of (R)‐ and (S)‐ricinoleic acid derivatives

“…The final concentration of DMSO in culture medium was 0.1%. The compound concentrations used in the performed tests were 5, 10, and 20 μM, and they were selected on the basis of results obtained in previous studies 19 …”

“…Human colon adenocarcinoma cells (HT29 cells) were purchased from the American Type Culture Collection (Rockville, MD, USA). This type of cells was chosen for experiments due to their high sensitivity to test compounds observed in previous experiments 19 . The cells were grown in RPMI growth medium supplemented with FBS (10%), penicillin/streptomycin solution (1%), and MEM nonessential‐amino acids solution (1%) in standard conditions at 37°C, with an atmosphere of 5% carbon dioxide and 95% air and with 100% humidity.…”

“…Dos Santos et al 17 reported that derivatives of RA and ethanolamine or pyrrolidine effectively inhibited growth of several cancer cell lines. Also, our earlier studies demonstrated that derivatives of RA and ethanolamine or pyrrolidine were cytotoxic against four cancer cell lines and normal human lymphocytes, but the pyrrolidine derivatives were less active than these of ethanolamine 19 . In the above mentioned studies, both enantiomers of RA derivatives were used.…”

“…In the present paper, we focused on enantiomers of RA amide derivatives synthesized with the use of ethanolamine or pyrrolinine for which the most promising cytotoxic effects were observed in terms of the anticancer potential 19 . The mechanism of their cytotoxicity is unknown, so we decided to study their ability to induce oxidative stress, DNA damage, and apoptosis.…”

Chiral amide derivatives of ricinoleic acid and 3-hydroxynonanoic acid synthesis and cytotoxic activity

“…Limited data on this compound result from the fact that it have not been identified yet in any natural source. However, in 2014 an efficient method for the preparation of (S)-RA was developed (Kula et al 2014), and then, its derivatives were obtained and described for the first time (Matysiak et al 2017(Matysiak et al , 2018.…”