Design, synthesis, cytotoxicity evaluation and molecular docking studies of 1,4-naphthoquinone derivatives

•Twenty-two 1,4-naphthoquinone derivatives were designed and synthesized.•New compounds were confirmed by different spectral techniques and X-ray crystallographic analysis.•Compound 3a exhibited the best activity against the Bel-7402 cells line.•Molecular docking studies showed that compound 3a could interact with both Topo-II and Bcr-Abl kinase. Coupling of two distinct pharmacophores, 1,4-naphthoquinone and benzoic acid, endowed with different biological properties, afforded twenty-two hybrid compounds to modulate both Topo-II and Bcr-Abl kinase. The structures of the compounds were characterized by 1H NMR, 13C NMR and HR-MS. The 1,4-naphthoquinone derivatives possessed the potent inhibitory activities against Bel-7402 cells. Among them, compound 3a exhibited the best activity against the Bel-7402 cells line with IC50 of 8.6 ± 3.09 µM (The IC50 of Cisplatin was 6.73 ± 0.37 µM). The SAR studies revealed that substituents on the benzoic acids played a crucial role in determining cytotoxicity of the hybrids. Molecular docking studies showed that the hybrid could interact with both Topo-II and Bcr-Abl kinase. These hybrids might serve as lead compounds for further developing new anticancer drugs. [Display omitted]