, vol. 138, pp. 565-576, 2017.
A series of novel pyrazolo[3,4-d]pyrimidines bearing benzenesulfonamide moiety 5a-f, 6 and 7 were
synthesized. Cytotoxic screening was conducted against MCF-7 and HepG2. 6-(4-Methoxyphenyl)-4-
oxopyrazolopyrimidine derivative 5e and 4-imino-6-oxopyrazolopyrimidine derivative 6 revealed
potent cytotoxic activity with IC50 1.4 mM (MCF-7) and 0.4 mM (HepG2), respectively compared to that of
doxorubicin, (IC50 ¼ 1.02 mM and 0.9 mM, respectively). Compounds 5e and 6 were subjected to cell cycle
analysis and apoptosis assay after 24 h and 48 h treatment. Compound 5e arrested cell at G1 phase, while
6 arrested cell at S and G2/M phases, respectively. The apoptotic effect of both compounds were evidenced
by pre G1 apoptosis as its percentage increased by time (7.38%, 11.61%) and (13.92%, 16.71%),
respectively. Apoptosis induction capability was confirmed by the effect on early and late apoptosis and
augmentation of caspase-3 level. Furthermore, compound 6 inhibited CDK2 enzyme with IC50 ¼ 0.19 mM
and increased levels of its regulators, P21 and P27 by 10.06% and 8.5%, respectively. Moreover, a molecular
docking study of compound 6 on CDK2 enzyme was adopted to explore binding interaction with
amino acid residues of its active site.
