Synthesis and Biological Evaluation of Lipophilic 1,4-Naphthoquinone Derivatives against Human Cancer Cell Lines

Abstract

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 OPEN ACCESS Molecules 2015, 20 11995 concentration-dependent manner. Taken together, compound 11a effectively inhibits colon cancer cell proliferation and may be a potent anticancer agent.

Cytotoxicity of Synthesized 1,4-Naphthoquinone Oxime Derivatives on Selected Human Cancer Cell Lines

“…1), including antibacterial, antitrypanosome, antiviral, antiparasitic, antiplasmodial, antiinflammatory, antiproliferative and antimalarial. [1][2][3][4][5] As proved by our group 6) and Ahn's team, 7) 6-substituted 5,8-dimethoxy-1,4-naphthoquinone (DMNQ) derivatives display a higher inhibitory efficiency on DNA topoisomerase-I and the cytotoxicity against cancer cells compared with the corresponding 2-substituted derivatives due to less steric hindrance on the naphthalene ring. 8) The main mechanisms of naphthoquinones acting inhibitory activity are ascribed to the generation of reactive oxygen species (ROS) and bioreductive alkylation.…”

Naphthoquinones of natural origin: Aqueous chemistry and coordination to half-sandwich organometallic cations

“…Naphthoquinones readily act as reducing agents leading to the formation of radicals and reactive oxygen species (ROS) [10]. In the past, several quinones and naphthoquinones were biologically tested and revealed cytostatic properties [6,7,[11][12][13]. Half-sandwich organometallic complexes containing 2-hydroxy- [1,4]-naphthoquinones as ligand scaffold have already been reported in literature with promising results [14][15][16].…”

Influence of lipophilicity in O‐acyl and O‐alkyl derivatives of juglone and lawsone: a structure–activity relationship study in the search for natural herbicide models

“…They generally contain hydroxyl and/or methyl groups as substituents, although they can also be found joined to monosaccharides. In addition to their properties as natural pigments, a broad range of biological activities have been described for these compounds, for example, antifungal, phytotoxic, anti‐inflammatory, antioxidant and anticancer properties . These effects are mainly ascribed to the ability of naphthoquinones to generate reactive oxygen species (ROS) and also the electrophilicity of the quinone moiety in reactions with different biological targets through a 1,4‐Michael addition involving the nucleophilic thiol species, proteins, DNA and RNA …”

“…In addition to their properties as natural pigments, a broad range of biological activities have been described for these compounds, for example, antifungal, phytotoxic, anti-inflammatory, antioxidant and anticancer properties. [1][2][3][4][5] These effects are mainly ascribed to the ability of naphthoquinones to generate reactive oxygen species (ROS) and also the electrophilicity of the quinone moiety in reactions with different biological targets through a 1,4-Michael addition involving the nucleophilic thiol species, proteins, DNA and RNA. [6][7][8][9][10] Plants that contain naphthoquinones have been used worldwide since ancient times to treat, for example, gastrointestinal disorders or herpes.…”