Abstract
To examine the effect of hydrophobicity on the anticancer activity of 1,4-naphthoquinone derivatives, a series of compounds bearing a 2-O-alkyl-, 3-C-alkyl- or 2/3-N-morpholinoalkyl group were synthesized and evaluated for their anticancer activity against five human cancer cell lines in vitro. The cytotoxicity of these derivatives was assayed against HT-29, SW480, HepG2, MCF-7 and HL-60 cells by the MTT assay. Among them, 2-hydroxy-3-farnesyl-1,4-naphthoquinone (11a) was found to be the most cytotoxic against these cell lines. Our results showed that the effectiveness of compound 11a may be attributed to its suppression of the survival of HT-29. Secondly, in the Hoechst 33258 staining test, compound 11a-treated cells exhibited nuclear condensation typical of apoptosis. Additionally, cell cycle analysis by flow cytometry indicated that compound 11a arrested HT-29 cells in the S phase. Furthermore, cell death detected by Annexin V-FITC/propidium iodide staining showed that compound 11a efficiently induced apoptosis of HT-29 in a concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent.
Highlights
Millions of lives are lost because of cancer in the world each year and the number is increasing.greater than 30% of cancers are preventable [1] and some forms of cancer are curable regardless of when they are diagnosed, while many others are only curable if discovered at an early stage
We synthesized and evaluated the effect of incorporation of new alkyl or terpenyl moieties in 1,4-naphthoquinones, including lawsone substituted at the 2-C/3-O-position with alkyl or terpenyl groups and juglone substituted at position 2/3-N-morpholinoalkyl groups, with the aim to analyze the influence of these substituents on the cytotoxicity of these derivatives against human cancer cell lines
1,4-naphthoquionone derivatives were synthesized from lawsone (2) with alkyl, terpenyl, alkylamino, or morpholinealkylamino moieties through 2-O- or 3-C-alkylation
Summary
Millions of lives are lost because of cancer in the world each year and the number is increasing. It was reported that monoterpenyl- and diterpenylnaphthoquinones derivatives had IC50 values in the micromolar range against several tumor cell lines [20]. These derivatives were synthesized through Diels-Alder addition of natural terpenoids and p-benzoquinones, followed by side chain transformation [21]. We synthesized and evaluated the effect of incorporation of new alkyl or terpenyl moieties in 1,4-naphthoquinones, including lawsone substituted at the 2-C/3-O-position with alkyl or terpenyl groups and juglone substituted at position 2/3-N-morpholinoalkyl groups, with the aim to analyze the influence of these substituents on the cytotoxicity of these derivatives against human cancer cell lines. We prepared and evaluated C-2 amino substituted 1,4-naphthoquinones, a core structure present in numerous naturally occurring bioactive quinones, such as mitomycin C, as well as some synthetic compounds [23]
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