Novel Glu-based pyrazolo[3,4-d]pyrimidine analogues: design, synthesis and biological evaluation as DHFR and TS dual inhibitors.

ABSTRACT: A novel series of multifunctional pyrazolo[3,4-d]pyrimidine-based glutamate analogs (6a-l and 7a,b) have been designed and synthesized as antifolate anticancer agents. Among the tested compounds, 6i exhibited the most potent anti-proliferative activity towards NSCLC, CNS, Ovarian, Prostate, Colon, Melanoma, Breast, and Renal cancers with good to weak cytostatic activity and non-lethal actions. 6i demonstrated higher selectivity for cancer than normal cells. 6i could significantly increase the accumulation of S-phase cells during the cell cycle distribution of cancer cells with high potency in the induction of apoptosis. The results unveiled that 6i probably acts through dual inhibition of DHFR and TS enzymes (IC₅₀ = 2.41 and 8.88 µM, cor

SUBMITTER: Mahnashi M 

PROVIDER: S-EPMC10120551 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature