New pyrazolo[3,4-d]pyrimidine derivatives as EGFR-TK inhibitors: design, green synthesis, potential anti-proliferative activity and P-glycoprotein inhibition.

ABSTRACT: In this study, four series of new pyrazolo[3,4-d]pyrimidine derivatives were designed and synthesized with both green and conventional methods. All the synthesized candidates were chemically confirmed using spectroscopic methods, and the DFT of the reaction mechanism was illustrated. The anti-proliferative activity of the synthesized compounds was evaluated against NCI 60 cancer cell lines. Two compounds (15 & 16) exhibited excellent broad-spectrum cytotoxic activity in NCI 5-log dose assays against the full 60-cell panel with GI₅₀ values ranging from 0.018 to 9.98 μM. Moreover, the enzymatic assessment of the most active derivatives 4, 15, and 16 against EGFR tyrosine kinase showed significant inhibitory activities with IC₅₀ of 0.054, 0.135, and 0.034 μM, resp

SUBMITTER: Hassaballah AI 

PROVIDER: S-EPMC10774712 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature