A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents

Figures & data

Figure 1. ORTEP Diagram of compound 3.

Scheme 1. A proposed mechanism for the reaction of 4-methylbenzenesulfonylhydrazide (1) with (E)-ethyl 2-cyano-3-ethoxyacrylate (2) at refluxing temperature.

Scheme 2. Preparation pathways for compounds 4–11.

Scheme 3. Preparation pathways for compounds 12–19.

Figure 2. In vitro cytotoxicity of the compounds 6a and 18 on human cancer cell line (HCT).

Figure 3. In vitro cytotoxicity of the compounds 6a and 18 on breast cancer cell line (MCF-7).

Table 1. Docking score, binding energy and IC₅₀ of the new compounds against mouse tumor model (EAC), HCT (colon) and MCF-7 (breast cancer cell lines).

Tested compounds	IC50 (µg/ml) (EAC)	IC50 (µg/ml) (HCT)	IC50 (µg/ml) (MCF-7)	Docking score	Binding energy
4	200			−6.6	−51.125
5	200			−1.5	−54.981
6a	85	29.58	24.34	−8.3	−56.097
7	200			−6.5	−55.761
9	191			−5.0	−46.954
10	144			−5.48	−57.263
12	186			−5.6	−44.426
15	180			−4.6	−63.754
18	33	10.8	10.24	−5.9	−87.567
19	200			−4.6	−56.904

Figure 4. Electrostatic and hydrogen bond interactions of compound 18 with active site of CDK2.

Figure 5. Schematic interaction of compound 18 with amino acids in the active pocket of CDK2.

Figure 6. Hydrogen bond interactions of compound 18 with active site of CDK2.