Novel pyrazolo[3,4-d]pyrimidines: design, synthesis, anticancer activity, dual EGFR/ErbB2 receptor tyrosine kinases inhibitory activity, effects on cell cycle profile and caspase-3-mediated apoptosis.

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  • Additional Information
    • Source:
      Publisher: Taylor & Francis Country of Publication: England NLM ID: 101150203 Publication Model: Print Cited Medium: Internet ISSN: 1475-6374 (Electronic) Linking ISSN: 14756366 NLM ISO Abbreviation: J Enzyme Inhib Med Chem Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basingstoke, UK : Taylor & Francis, c2002-
    • Subject Terms:
    • Abstract:
      A series of novel pyrazolo[3,4-d]pyrimidines was synthesised. Twelve synthesised compounds were evaluated for their anticancer activity against 60 human tumour cell lines by NCI (USA). Compound 7d proved prominent anticancer activity. It showed 1.6-fold more potent anti-proliferative activity against OVCAR-4 cell line with IC 50 = 1.74 μM. It also exhibited promising potent anticancer activity against ACHN cell line with IC 50 value 5.53 μM, representing 2.2-fold more potency than Erlotinib. Regarding NCI-H460 cell line, compound 7d (IC 50 = 4.44 μM) was 1.9-fold more potent than Erlotinib. It inhibited EGFR and ErbB2 kinases at sub-micromolar level (IC 50 = 0.18 and 0.25 µM, respectively). Dual inhibition of EGFR and ErbB2 caused induction of apoptosis which was confirmed by a significant increase in the level of active caspase-3 (11-fold). It showed accumulation of cells in pre-G1 phase and cell cycle arrest at G2/M phase.
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    • Contributed Indexing:
      Keywords: EGFR; ErbB2; Pyrazolo[3,4-d]pyrimidines; anticancer activity; apoptosis; caspase-3; cell cycle arrest profile; design; synthesis
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Protein Kinase Inhibitors)
      0 (Pyrazoles)
      0 (Pyrimidines)
      EC 2.7.10.1 (EGFR protein, human)
      EC 2.7.10.1 (ErbB Receptors)
      EC 2.7.10.1 (Receptor, ErbB-2)
      EC 3.4.22.- (CASP3 protein, human)
      EC 3.4.22.- (Caspase 3)
    • Publication Date:
      Date Created: 20190129 Date Completed: 20190507 Latest Revision: 20200225
    • Publication Date:
      20240104
    • Accession Number:
      PMC6352943
    • Accession Number:
      10.1080/14756366.2018.1564046
    • Accession Number:
      30688116