title: 4-Substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives: design, synthesis, antitumor and EGFR tyrosine kinase inhibitory activity.
abstract: Four series of some 4-substituted-1-phenyl-1H-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.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
authors.forename: Safinaz E-S
authors.initials: SE
authors.lastname: Abbas
authors.forename: Enayat I
authors.initials: EI
authors.lastname: Aly
authors.forename: Fadi M
authors.initials: FM
authors.lastname: Awadallah
authors.forename: Walaa R
authors.initials: WR
authors.lastname: Mahmoud
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C014175:pyrazolo(3,4-d)pyrimidine; D000255:Adenosine Triphosphate; D066246:ErbB Receptors
keywords: EGFR-TK inhibition; antitumor; molecular modeling; pyrazolo[3,4-d]pyrimidines; synthesis