title: Synthesis and biological evaluation of bile carboxamide derivatives with pro-apoptotic effect on human colon adenocarcinoma cell lines.
abstract: 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.
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR des Sciences Pharmaceutiques, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), CNRS INC3M - SFR ICORE 146, Bd Becquerel, F-14032 Caen Cedex, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Brossard
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR de Médecine, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT, EA 4652), SFR ICORE 146, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Lechevrel
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR des Sciences Pharmaceutiques, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), CNRS INC3M - SFR ICORE 146, Bd Becquerel, F-14032 Caen Cedex, France. Electronic address: laila.elkihel@unicaen.fr.
authors.forename: Laïla
authors.initials: L
authors.lastname: El Kihel
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR de Médecine, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT, EA 4652), SFR ICORE 146, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Quesnelle
authors.affiliation: Université Hassan Premier, Faculté des Sciences et Techniques, Km 3, Route de Casablanca, BP 577, 26000 Settat, Morocco.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Khalid
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR de Médecine, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT, EA 4652), SFR ICORE 146, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
authors.forename: Safa
authors.initials: S
authors.lastname: Moslemi
authors.affiliation: Université de Caen/Basse-Normandie, Esplanade de la Paix, 14032 Caen Cedex, France; UFR de Médecine, Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT, EA 4652), SFR ICORE 146, Avenue de la Côte de Nacre, 14032 Caen Cedex, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Reimund
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D001647:Bile Acids and Salts
keywords: Apoptosis; Bile carboxamide derivatives; Colorectal cancer; Cytotoxicity; Piperazinyl steroids