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Synthesis, docking study and antitumor evaluation of certain newly synthesized pyrazolo[3,4-d]pyrimidine derivatives

Khaled R.A.Abdellatif, Eman K.A.Abdelall,Mohamed A.Abdelgawad, Rasha R.Ahmed, Rania B.Bakr ,

A series of new4-substituted amino-1H-pyrazolo[3,4-d]pyrimidines (6a-e) and (8a-e) was synthesized using ethyl 5-amino-3-methyl-1-phenyl-1Hpyrazole- 4-carboxylate (1) as the startingmaterial. The cytotoxic activity of the newly synthesized compounds against human breast adenocarcinoma (MCF-7) cell line was investigatd. Most of the tested compounds showed potent to moderate growth inhibitory activity, especially 3,6-dimethyl-1- phenyl-4-[3-(1-acetyl-5—(4-fluorophenyl)-4,5-dihydro-1H-pyrazol-3- yl)anilino]-1H-pyazolo[3,4-d]pyrimidine (8b) exhibited the highest activity among the tested compounds with IC50% equal to 28.157 µg/mL. Docking the synthesized compounds into the epidermal growth factor receptor (EGFR),which is highly expressed in breast cancer,was performed to explore the possible interactions of these compounds with the EGFR. The activity of the reported compounds supports its clinical promise as a component of therapeutic stratiges for cancer, for which high concentration of chemotherapeutic agents are always a major limitation.