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4‐Substituted‐1‐phenyl‐1 H ‐pyrazolo[3,4‐ d ]pyrimidine Derivatives: Design, Synthesis, Antitumor and EGFR Tyrosine Kinase Inhibitory Activity
Author(s) -
Abbas Safinaz E.S.,
Aly Enayat I.,
Awadallah Fadi M.,
Mahmoud Walaa R.
Publication year - 2015
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12451
Subject(s) - pyrimidine , chemistry , stereochemistry , pyrazole , docking (animal) , cell culture , inhibitory postsynaptic potential , structure–activity relationship , in vitro , biochemistry , biology , medicine , nursing , neuroscience , genetics
Four series of some 4‐substituted‐1‐phenyl‐1 H ‐pyrazolo[3,4‐ d ]pyrimidine derivatives 5a – f , 6a – f , 8a – f , and 9a – f were designed to be screened for their antitumor activity. All compounds were evaluated against breast ( MCF ‐7) and lung ( A ‐549) cell lines. Six compounds 5a , 5b , 6b , 6e , 9e , and 9f displaying activity against both cell lines were further estimated for their EGFR ‐ TK inhibitory activity where they revealed 41–91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP ‐binding site of EGFR ‐ TK demonstrated their binding mode where H ‐bonding interaction with Met793 through N 1 of pyrimidine or N 2 of pyrazole was observed.