Synthesis and biological evaluation of bile carboxamide derivatives with pro-apoptotic effect on human colon adenocarcinoma cell lines.
Fiche publication
Date publication
octobre 2014
Journal
European journal of medicinal chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr REIMUND Jean-Marie
Tous les auteurs :
Brossard D, Lechevrel M, El Kihel L, Quesnelle C, Khalid M, Moslemi S, Reimund JM
Lien Pubmed
Résumé
We previously reported that the cinnamylpiperazinyl group in the side chain of the chenodeoxycholic acid showed apoptosis-inducing activity on multiple myeloma cancer cell line KMS-11. In the present study, we synthesized and tested the pro-apoptotic potency of fifteen new piperazinyl bile carboxamide derived from cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic and lithocholic acids on human colon adenocarcinoma cell lines DLD-1, HCT-116, and HT-29. Cell viability was first measured using XTT assay. The most of the synthetic bile carboxamide derivatives decreased significantly cell viability in a dose-dependent manner. HCT-116 and DLD-1 cell lines were more sensitive than HT-29 to tested compounds. 9c, 9d showed the best in vitro results in term of solubility and dose-response effect on the three colon adenocarcinoma cell lines. Additionally, flow cytometric and Western-blotting analysis showed that 9c induced pro-apoptosis in DLD-1 and HCT-116 whereas 9d did not. We conclude that the benzyl group improved anti-proliferative activity and that the α-hydroxyl group was found to be more beneficial at the 7-position in steroid skeleton.
Mots clés
Apoptosis, Bile carboxamide derivatives, Colorectal cancer, Cytotoxicity, Piperazinyl steroids
Référence
Eur J Med Chem. 2014 Oct 30;86:279-90