Biological profile of new apoptotic agents based on 2,4-pyrido[2,3-d]pyrimidine derivatives.
In order to obtain less toxic antitumoral compounds we have looked for novel compounds with anticancer activity based on proapoptotic mechanisms. The compounds studied in this work are derivatives of bicyclic aromatic systems like pyrido[2,3-d]pyrimidines. The potential antitumoral activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer lines (MD-MBA-231, HT-29, and T-24). The data indicate that HC-6 is a potent anticancer drug showing dose-dependent cytostatic and proapoptotic effects through activation of two different signaling pathways namely a pathway leading to cell cycle arrest and a transcription-independent route leading to rapid apoptosis.
Cordeu
Lucía
L
Laboratorio de Farmacogenómica, Area de Oncología, Centro de Investigación Médica Aplicada, Pamplona, Spain. lcorver@alumni.unav.es
Cubedo
Elena
E
Bandrés
Eva
E
Rebollo
Amaia
A
Sáenz
Xabi
X
Chozas
Hector
H
Victoria Domínguez
Ma
M
Echeverría
Mikel
M
Mendivil
Beatriz
B
Sanmartin
Carmen
C
Palop
Juan Antonio
JA
Font
María
M
García-Foncillas
Jesús
J
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology
D000970:Antineoplastic Agents; D011743:Pyrimidines