Dual Kinase Inhibition of EGFR/HER2: Design, Synthesis and Molecular Docking of Thiazolylpyrazolyl-Based Aminoquinoline Derivatives as Anticancer Agents**

Two new series of aminoquinoline based derivatives (thiazolyl pyrazolines and pyrazolyl thiazolidinones) were designed and synthesized. The in vitro antiporliferative activity of the target compounds was assessed against two different cancer types; (MCF-7) breast cancer cell line and (HCT116) colorectal carcinoma cell line, using MTT assay technique. The 4-methyl thiazolyl pyrazoline derivative 4 b showed potent anticancer activity on HCT116 with IC50 value of 3.07 mu M. The promising derivative exhibited dual kinase EGFR/HER2 inhibitory activity with IC50 values of 0.06/0.08 mu M versus 0.04/0.05 mu M for erlotinib and lapatinib, respectively, as detected by EGFR and HER2 kinase assays. Moreover, the flow cytometry analysis of HCT116 cells treated with 4 b revealed that the derivative was capable of arresting the cell cycle at G1 phase and inducing late cellular apoptosis. Molecular docking of 4 b showed that the synthesized compound exhibited promising binding energy scores of -15.0774 and -16.9040 kcal/mol into EGFR and HER2 active sites, respectively. Finally, the pharmacokinetics and physicochemical parameters of 4 b showed its promising drug-like properties.