Twelve novel quinazolinone–pyrimidine hybrids were synthesized, of which some of them showed dual functions as DPP-4 inhibitors and anti-cancer agents.

Fifteen derivatives of spirooxindole-4H-pyran (A 1 -A 15 ) were subjected to evaluate through intravenous infusion of pentylenetetrazole (PTZ) induced epilepsy mouse models. Four doses of the compounds (20, 40, 60, 80 mg/kg) were tested in comparison to diazepam as positive control. The resulted revealed that compounds A 3 and A 12 were the most active compounds and indicated signi cant anticonvulsant activity in the PTZ test. The tested compounds were prepared via a multicomponent reaction using graphene oxide (GO) based on the 1-(2-aminoethyl) piperazine as a novel heterogeneous organocatalyst. The prepared catalyst (GO-A.P.) was characterized using some diverse microscopic and spectroscopic procedures as well. The results showed high catalytic activity of the catalyst in the synthesis of spirooxindole-4H-pyran derivatives. The GO-A.P. catalyst was reusable at least for 5 times with no signi cant decrease in its catalytic action. In silico assessment of physico chemical activity of all compounds also were done which represented appropriate properties. Finally, molecular docking study was performed to achieve their binding a nities as γ-aminobutyric acid-A (GABA-A) receptor agonists as a plausible mechanism of their anticonvulsant action. Binding free energy values of the compounds represented strongly matched with biological activity.

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Thirteen novel isatin-ampyrone Schiff bases derivatives were synthesized in only two steps of 70%-90% overall yields. In vitro cytotoxic activity of these new Schiff bases against three human tumor cell lines (MCF-7, A549, and SCOV3) as well as normal breast cell line (MCF-10A) were evaluated by MTT assay. Structure-activity relationship of the tested compounds revealed that chlorine group at C-5 position of the isatin ring significantly increased the cytotoxic activity. This study generally led to introduce a highly active molecule (M 12 ) with IC 50 values of 5.12, 25.5, and 12.9 μΜ, on MCF-7, A549, and SCOV3, respectively. Furthermore, molecular docking studies of the synthesized compounds were also done to investigate their binding modes towards VEGFR-2 and JNK3-MAP kinase as the main targets for isatin-containing anticancer agents. Binding free energy values of the compounds showed positive correlation with their cytotoxic activities. To confirm the docking results, molecular docking simulations of potent compound (M 12 ) against VEGFR-2 and JNK3 MAP kinase were also performed. According to the cytotoxic results and in silico ADMET predictions together, M 12 can be considered as a potent candidate for the future anticancer studies.