Design, Synthesis, Anti-cancer Screening, Mechanistic, and Molecular Modeling Studies of N-(3-methoxyphenyl)-2-(4-oxo-1-phenyl-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl) Acetamide.

Kobesy, Mostafa Roshdy

doi:10.21608/mermj.2025.380096.1025

Design, Synthesis, Anti-cancer Screening, Mechanistic, and Molecular Modeling Studies of N-(3-methoxyphenyl)-2-(4-oxo-1-phenyl-1,4-dihydro-5H-pyrazolo[3,4-d]pyrimidin-5-yl) Acetamide.

Document Type : Original Article

Author

Mostafa Roshdy Kobesy

Pharmaceutical chemistry, pharmacy, merit, Sohag, Egypt

10.21608/mermj.2025.380096.1025

Abstract

A novel compound of pyrazolo[3,4-d]pyrimidinone derivative was synthesized, characterized, and screened for its anti-cancer activity. Results showed that the target compound exhibited potent anti-cancer activity against the renal RXF-393 cancer cell line with complete inhibition of growth and against the non-small cell lung (NSCL) HOP-92 cancer cell line with a growth inhibition percent of 91.04%. Importantly, the target compound has a higher safety profile towards the normal cell line WI 38 than the staurosporine with IC50 values of 44.893±2.55 µM and 13.610±0.77 µM, respectively, which reflect the selectivity of the target compound toward the cancer cell lines rather than the normal cell lines. Also, a mechanistic study for the target compound showed potent activity against CDK1 and CDK2 with IC50 values of 0.385±0.021 µM and 0.58±0.018 µM, respectively, in comparison to the reference roscovitine with IC50 values of 0.803±0.044 µM and 1.072±0.033 µM. Molecular modeling investigations of the target compound validated strong connections with the obtained biological outcome Furthermore, the evaluated molecule exhibited favorable drug-likeness and appropriate physicochemical characteristics. These results suggest that the target molecule may be a good candidate for the production of novel anti-cancer agents.

Keywords