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.
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Proliferation / drug effects
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Drug Design*
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Drug Screening Assays, Antitumor
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Humans
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Molecular Docking Simulation
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Molecular Structure
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Naphthoquinones / chemical synthesis
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Naphthoquinones / chemistry
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Naphthoquinones / pharmacology*
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Structure-Activity Relationship
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Tumor Cells, Cultured
Substances
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Antineoplastic Agents
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Naphthoquinones
Grants and 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].