15013-16-8Relevant articles and documents
The compound 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone induces apoptosis via reactive oxygen species-regulated mitogen-activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells
Wang, Jia-Ru,Shen, Gui-Nan,Luo, Ying-Hua,Piao, Xian-Ji,Shen, Meng,Liu, Chang,Wang, Yue,Meng, Ling-Qi,Zhang, Yi,Wang, Hao,Li, Jin-Qian,Xu, Wan-Ting,Liu, Yang,Sun, Hu-Nan,Han, Ying-Hao,Jin, Mei-Hua,Cao, Long-Kui,Jin, Cheng-Hao
, p. 295 - 306 (2018)
(Table presented.). It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.
6-Substituted 1,4-Naphthoquinone Oxime Derivatives (III): Synthesis and Cytotoxic Evaluation
Huang,Liu,Meng,Li
, p. 1025 - 1035 (2018)
As a continuous study, a set of 23 new 6-substituted 1,4-naphthoquinone oxime derivatives are synthesized and screened for their in vitro cytotoxic activity. Four of those oxime derivatives demonstrate more potent cytotoxic activity towards K562, HCT-15, and HCT-116 cell lines than a reference drug 5-Fu. In particular, compound 21g exhibits the strongest inhibitory activity against K562 cell lines with IC50 values of 1.25 μM. According to flow cytometry data, compound 21g can arrest cell cycle at S phase and induce a strong apoptotic response in K562 cells. The preliminary structure-activity relationship study shows that the nature of substituents in positions 6 and 1' of 1,4-naphthoquinone derivatives significantly affect their cytotoxic activity.
The design of 1,4-naphthoquinone derivatives and mechanisms underlying apoptosis induction through ROS-dependent MAPK/Akt/STAT3 pathways in human lung cancer cells
Zhang, Yi,Luo, Ying-Hua,Piao, Xian-Ji,Shen, Gui-Nan,Wang, Jia-Ru,Feng, Yu-Chao,Li, Jin-Qian,Xu, Wan-Ting,Zhang, Yu,Zhang, Tong,Wang, Chang-Yuan,Jin, Cheng-Hao
, p. 1577 - 1587 (2019)
The natural compound 1,4-naphthoquinone has potent anti-tumor activity. However, the clinical application of 1,4-naphthoquinone and its derivatives has been limited by their side effects. In this study, we attempted to reduce the toxicity of 1,4-naphthoquinone by synthesizing two derivatives: 2,3-dihydro-2,3-epoxy-2-propylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (EPDMNQ) and 2,3-dihydro-2,3-epoxy-2-nonylsulfonyl-5,8-dimethoxy-1,4-naphthoquinone (ENDMNQ). Then we evaluated the cytotoxicity and molecular mechanisms of these compounds in lung cancer cells. EPDMNQ and ENDMNQ significantly inhibited the viabilities of three lung cancer cell lines and induced A549 cell cycle arrest at the G1 phase. In addition, they induced the apoptosis of A549 lung cancer cells by increasing the phosphorylation of p38 and c-Jun N-terminal kinase (p-JNK), and decreasing the phosphorylation of extracellular signal-related kinase (p-ERK), protein kinase B (Akt), and signal transducer and activator of transcription 3 (STAT3). Furthermore, they increased reactive oxygen species (ROS) levels in A549 cells; however, pretreatment with the ROS inhibitor N-acetyl-L-cysteine significantly inhibited EPDMNQ- and ENDMNQ-mediated apoptosis and reversed apoptotic proteins expression. In conclusion, EPDMNQ and ENDMNQ induced G1 phase cell cycle arrest and apoptosis in A549 cells via the ROS-mediated activation of mitogen activated protein kinase (MAPK), Akt and STAT3 signaling pathways.
Enantioselective Total Syntheses of (R)- A nd (S)-Naphthotectone, and Stereochemical Assignment of the Natural Product
Guerrero-Vásquez, Guillermo A.,Galarza, Flávia A. D.,Molinillo, José M. G.,Andrade, Carlos Kleber Z.,Macías, Francisco A.
, p. 1599 - 1604 (2016/04/05)
Both isomers of naphthotectone, an isoprenoid quinone from Verbenaceae Tectona grandis possessing interesting biological activities, were enantioselectively obtained by two different synthetic routes in which the carbon side-chain of the naphthoquinone core was introduced using either a Sonogashira or a Heck coupling reaction. In both cases, the naphthoquinone core of the final products was obtained by a late-stage anodic treatment. (R)-Naphthotectone was obtained in six steps from leuconaphthazarin with an overall yield of 38 % and an enantiomeric excess of 86 %. This compound was found to have the same absolute configuration as the natural product at its C-3′ stereogenic center. (S)-Naphthotectone was obtained in five steps from leuconaphthazarin with an overall yield of 36 % and an enantiomeric excess of 80 %. Naphthotectone was synthesized in both racemic and enantioenriched forms by two different synthetic strategies using Pd coupling reactions and anodic treatment as key steps. The stereochemistry of the natural product has been assigned.
