Abstract
The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.
Highlights
Cancer is considered a serious health hazard problem
The docking simulation for the ligand was carried out using molecular operating environment (MOE) software supplied by the Chemical Computing Group, Inc., Montreal, QC, Canada [14]
After incubation of the cells with compound 7 for 24 h, the results showed that there is no significant effect of the treatment with the compound on the viability of A549 cells through apoptosis in comparison to the untreated group
Summary
Cancer is considered a serious health hazard problem. cancer is ranked the second cause of recorded deaths in the world. Ibrutinib is a pyrazolopyrimidine-based kinase inhibitor, wh2iocfh has been studied for the treatment of B-cell cancers [8]. The abovementioned findings led to the design and synthesis of a group of compounds that comprise the pyrazolo[3,4-d]pyrimidine scaffold linked to a piperazine moiety, bearing different aromatic nuclei through different amide linkages (compounds of the general formulas B and C; Figure 1), as well as to tests of their anticancer activity [10]. The study tested the effect of such an action on treating type 2 diabetes mellitus (T2DM) It was the goal of this study to design and synthesize a group of compounds that comprise the N-aryl pyrazolo[3,4-d]pyrimidine scaffold having different arylidenehydrazino substitution at the 3-, 4- and 5-positions (compounds 5–7) and to test their. Cholesterol (mg/dL) Triglyceride (mg/dL) Bilirubin (mg/dL) Albumin (mg/dL) ALT (U/L) AST (U/L) ALP (U/L) Urea (U/L) Creatinine (mg/dL)
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