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Synthesis and Biological Evaluation of 2,4,6‐Functionalized Derivatives of Pyrido[2,3‐ d ]pyrimidines as Cytotoxic Agents and Apoptosis Inducers
Author(s) -
Sanmartín Carmen,
Domínguez María Victoria,
Cordeu Lucía,
Cubedo Elena,
GarcíaFoncillas Jesús,
Font María,
Palop Juan Antonio
Publication year - 2008
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200700133
Subject(s) - cytotoxic t cell , cytotoxicity , apoptosis , chemistry , cell culture , in vitro , pyrimidine , stereochemistry , biochemistry , biology , genetics
In the search for new derivatives with anticancer activity that are able to induce a selective pro‐apoptotic mechanism in cancer cells, we have designed, synthesized, and evaluated a series of new 2‐(alkylsulfanyl)‐ N ‐alkylpyrido[2,3‐ d ]pyrimidine‐4‐amine derivatives as cytotoxic and apoptosis inducers. The potential antitumor activity of the compounds was evaluated in vitro by examining their cytotoxic effects against human breast, colon, and bladder cancer‐cell lines. The IC 50 values of the compounds that showed cytotoxic activity were calculated. The cytotoxic compounds were then tested for their ability to induce caspase‐3 activation and nuclear‐chromatin degradation. Some compounds, such as 6c , 6d , 6e , 6j , 6o , and 6p , show significant in‐vitro cytotoxicity in at least two of the three tested cell lines, induced apoptosis, and also produced a rapid dose‐dependent increase in the caspase‐3 level in some of the cell lines tested. In order to test the selectivity of the compounds, two non‐tumoral human cell lines were used. Several compounds of the did not show cytotoxicity in these cell lines.