Design, synthesis and anticancer activity of naphthoquinone derivatives

Abstract

Basis on molecular docking and pharmacophore analysis of naphthoquinone moiety, a total of 23 compounds were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC₅₀ against SGC-7901 was 4.1 ± 2.6 μM. Meanwhile the anticancer mechanism of compound 12 had been investigated by AnnexinV/PI staining, immunofluorescence, Western blot assay and molecular docking. The results indicated that this compound might induce cell apoptosis and cell autophagy through regulating the PI3K signal pathway.

Keywords:

• Naphthoquinone moiety
• anticancer activity
• autophagy

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors thank the National Natural Science Foundation of China [Nos. 21977001 and 21602029], the Horizontal cooperation project of Fuyang municipal government [Nos. XDHX201722 and XDHX2016026], Anhui Province Foundation [No. 18030701213], Horizontal cooperation project of Yifan Pharmaceutical Co., Ltd [HX2019033], and Technological Fund of Fuyang normal university [2017FSKJ16].