Synthesis of bile acid derivatives and in vitro cytotoxic activity with pro-apoptotic process on multiple myeloma (KMS-11), glioblastoma multiforme (GBM), and colonic carcinoma (HCT-116) human cell lines.
The novelty of this work derives from the use of nitrogenous heterocycles as building block in the synthesis of conjugate bile acid derivatives. New piperazinyl bile acid derivatives were synthesized and tested in vitro against various human cancer cells (GBM, KMS-11, HCT-116). The best pro-apoptotic activity was obtained with N-[4N-cinnamylpiperazin-1-yl)-3alpha,7beta-dihydroxy-5beta-cholan-24-amide (7b) and N-[4N-cinnamyllpiperazin-1-yl)- 3alpha,7alpha-dihydroxy-5beta-cholan-24-amide (7c) on these human cancer cell lines (IC(50): 8.5-31.4microM). This activity was associated with nuclear and DNA fragmentation, demonstrating that 7b induces cell death by an apoptotic process as 7c. This study shows the possibility of hydrid heterocycle-steroids as new anticancer agents with improved bioactivity and easy to synthesize.
Brossard
Dominique
D
Centre d'Etudes et de Recherche sur le Médicament de Normandie, UPRES EA-4258, FR CNRS INC3M, Université de Caen Basse-Normandie, U.F.R. des Sciences Pharmaceutiques, Boulevard Becquerel, 14032 Caen Cedex, France.
El Kihel
Laïla
L
Clément
Monique
M
Sebbahi
Walae
W
Khalid
Mohamed
M
Roussakis
Christos
C
Rault
Sylvain
S
D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry
D001647:Bile Acids and Salts; D010879:Piperazines; D000077489:Piperazine