40815-76-7

Upstream product

• 556-56-9 allyl iodid 
• 36417-25-1 2-hydroxy-1,4-naphthoquinone silver salt 
• 106-95-6 allyl bromide 
• 5813-57-0 2-acetyl-1,4-naphthoquinone 
• 24850-33-7 allyltributylstanane 
• 762-73-2 trimethyl(allyl)stannane 
• 83-72-7 2-hydroxynaphtho-1,4-quinone 
• 615-91-8 2-hydroxy-5-methyl-1,4-benzoquinone 
• 107-18-6 allyl alcohol 
• 3724-55-8 methyl but-3-enoate 
• 1760-68-5 2-hydroxy-5,6-dimethylcyclohexa-2,5-diene-1,4-dione 
• 40815-72-3 2-allyloxy-1,4-naphthoquinone 
• 14777-30-1 2-propionyl-1,4-naphthoquinone 

Downstream Products

• 17112-93-5 2-methylnaphtho<1,2-b>furan-4,5-dione 

Relevant academic research and scientific papers

Palladium-catalyzed allylation of 2-hydroxy-1,4-naphthoquinone: Application to the preparation of lapachol

The Pd(PPh3)4-catalyzed reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with allyl alcohols and allyl esters offers an easy access to 3-allyl-2-hydroxy-1,4-naphthoquinones, compounds with interesting biological activity. The reaction finds application in the preparation of lapachol. Other 2-hydroxy-1,4-benzoquinones give allylation products in low yields. Georg Thieme Verlag Stuttgart.

Naphthofuran o-quinone compound, preparation method and application thereof, anti-tumor pharmaceutical composition and antibacterial pharmaceutical composition

The invention provides a naphthofuran o-quinone compound, a preparation method and application thereof, an anti-tumor pharmaceutical composition and an antibacterial pharmaceutical composition, and belongs to the technical field of medicine synthesis. The naphthofuran o-quinone compound provided by the invention shows good anti-tumor and antibacterial effects on the cellular level, and has good anti-tumor activity and antibacterial activity. The result of the embodiment shows that the in-vitro anti-tumor activity of the naphthofuran o-quinone compound provided by the invention is similar to or stronger than that of adriamycin, and the naphthofuran o-quinone compound has the potential of becoming a novel anti-tumor drug; the antibacterial activity of part of the compound is close to that of positive drugs, and the compound has the potential of becoming a new antibacterial drug with excellent curative effects; and the anti-tumor and antibacterial effects of the compound have important application value in the pharmaceutical industry.

Design, synthesis, and evaluation of proliferation inhibitory activity of novel L-shaped ortho-quinone analogs as anticancer agents

In this study, we present the design and synthesis of novel fully synthetic L-shaped ortho-quinone analogs with tanshinone IIA as the lead compoud, which is a molecule with numerous pharmacological benefits and potential to treat life-threatening diseases, such as cancer and viral infections. 24 L-shaped ortho-quinone analogs were designed and synthesized via click chemistry and introduced 1,2,3-triazole at the C-2 terminal of the furan ring. The cytotoxicity of these analogs toward different cancer cell lines was investigated in vitro. The new TD compounds showed potent inhibitory activities toward prostate cancer (PC3), leukemia (K562), breast cancer (MDA-231), lung cancer (A549), and cervical cancer (Hela) cell lines. Among them, TD1, TD11, and TD17 showed excellent broad-spectrum cytotoxic effects on five cancer cell lines by inducing apoptosis and arresting the cell cycle phase. Besides, TD1, TD11, and TD17 could target-bind with NQO1 protein in the prostate cancer cells PC3 leukemia cells K562. The results showed that removing the methyl group at C-3 and introducing 1,2,3-triazoles at the C-2 terminal of the furan ring were effective strategies for improving the broad-spectrum anticancer activity of L-shaped ortho-quinone analogs.

Molecular mechanism of action of new 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles with cytotoxic and selective effect against oral squamous cell carcinoma

The oral squamous cell carcinoma (OSCC) stands out as a public health problem due to its high incidence and low survival rate, despite advances in diagnosis and treatment. Moreover, the most commonly chemotherapeutic agents for OSCC, such as carboplatin and cisplatin, generate important side effects, evidencing the urgency in developing new drugs. Naphthoquinones are an important class of natural products or synthetic compounds with cytotoxic effect demonstrated on different cancer types. In the present study, thirty-five 1,4-naphthoquinones tethered to 1,2,3-1H-triazoles were synthesized and the antitumor activity and molecular mechanisms were evaluated in several assays including in vitro and in vivo models of OSCC and normal oral human cells. Compounds 16a, 16b and 16 g were able to induce cytotoxicity in three different tumor cell lines of human OSCC (SCC4, SCC9 and SCC25) and were more toxic and selective to tumor cells (Selective Index, SI > 2) than classical and chemically similar controls (Carboplatin and Lapachol). Compound 16 g showed the higher SI value. Besides, compounds 16a, 16b and 16 g significantly reduced colony formation of SCC9 cells in the tested concentrations. Hemolytic assay using compounds 16a, 16b and 16 g at high concentrations showed no compound exhibited hemolysis higher than 5%, similar to controls. In vivo acute toxicity study showed that 16 g was the only one, among the three compounds, with no apparent limiting toxic effects on mice in the tested concentrations. Thus, the investigation of cell death mechanisms was conducted with this compound. 16 g does not trigger ROS production nor binds to DNA. On the other hand, compound 16 g induced microtubule disorganization, and molecular modeling studies suggests a potential mechanism of action related to inhibition of topoisomerases and/or hPKM2 activities. Cell morphology, pyknotic nuclei presence, cleaved caspase-3 staining and viability assays using caspase-3 inhibitors demonstrate compound 16 g induced cell death through apoptosis. Among the 35 synthesized triazole naphthoquinones, compound 16 g was the most effective compound against OSCC cells, presenting high cytotoxicity (~35 μM), selectivity (SI ~ 6) and low acute toxicity on animals, and therefore might be considered for future cancer therapy.

Potent cytotoxicity of novel L-shaped ortho-quinone analogs through inducing apoptosis

Twenty-seven L-shaped ortho-quinone analogs were designed and synthesized using a one pot double-radical synthetic strategy followed by removing methyl at C-3 of the furan ring and introducing a diverse side chain at C-2 of the furan ring. The synthetic derivatives were investigated for their cytotoxicity activities against human leukemia cells K562, prostate cancer cells PC3, and melanoma cells WM9. Compounds TB1, TB3, TB4, TB6, TC1, TC3, TC5, TC9, TC11, TC12, TC14, TC15, TC16, and TC17 exhibited a better broad-spectrum cytotoxicity on three cancer cells. TB7 and TC7 selectively displayed potent inhibitory activities on leukemia cells K562 and prostate cancer cells PC3, respectively. Further studies indicated that TB3, TC1, TC3, TC7, and TC17 could significantly induce the apoptosis of PC3 cells. TC1 and TC17 significantly induced apoptosis of K562 cells. TC1, TC11, and TC14 induced significant apoptosis of WM9 cells. The structure-activity relationships evaluation showed that removing methyl at C-3 of the furan ring and introducing diverse side chains at C-2 of the furan ring is an effective strategy for improving the anticancer activity of L-shaped ortho-quinone analogs.

A novel tanshinone analog exerts anti-cancer effects in prostate cancer by inducing cell apoptosis, arresting cell cycle at G2 phase and blocking metastatic ability

Prostate cancer (PCa), an epithelial malignant tumor, is the second common cause of cancer death among males in western countries. Thus, the development of new strategies is urgently needed. Tanshinones isolated from Salvia miltiorrhiza and its synthetic analogs show various biological activities including anticancer effects. Among them, the tanshinone analog 2-((Glycine methyl ester)methyl)-naphtho (TC7) is the most effective, with better selectivity and lower toxicity. Therefore, in this work, the effect of TC7 against PCa was investigated through assessing the molecular mechanisms regulating the growth, metastasis, and invasion of PCa cells. Human PCa cells, PC3 and LNCAP, were used to evaluate TC7 mechanisms of action in vitro, while male BALB/c nude mice were used for in vivo experiments by subjecting each mouse to a subcutaneous injection of PC3 cells into the right flank to evaluate TC7 effects on tumor volume. Our in vitro results showed that TC7 inhibited cell proliferation by arresting the cell cycle at G2/M through the regulation of cyclin b1, p53, GADD45A, PLK1, and CDC2/cyclin b1. In addition, TC7 induced cell apoptosis by regulating apoptosis-associated genes such as p53, ERK1, BAX, p38, BCL-2, caspase-8, cleaved-caspase-8, PARP1, and the phosphorylation level of ERK1 and p38. Furthermore, it decreased DNA synthesis and inhibited the migration and invasion ability by regulating VEGF-1 and MMP-9 protein expression. Our in vivo evidence supports the conclusion that TC7 could be considered as a potential promising chemotherapeutic candidate in the treatment of PCa.

Lawsone, Juglone, and β-Lapachone Derivatives with Enhanced Mitochondrial-Based Toxicity

Naphthoquinones are among the most active natural products obtained from plants and microorganisms. Naphthoquinones exert their biological activities through pleiotropic mechanisms that include reactivity against cell nucleophiles, generation of reactive oxygen species (ROS), and inhibition of proteins. Here, we report a mechanistic antiproliferative study performed in the yeast Saccharomyces cerevisiae for several derivatives of three important natural naphthoquinones: lawsone, juglone, and β-lapachone. We have found that (i) the free hydroxyl group of lawsone and juglone modulates toxicity; (ii) lawsone and juglone derivatives differ in their mechanisms of action, with ROS generation being more important for the former; and (iii) a subset of derivatives possess the capability to disrupt mitochondrial function, with β-lapachones being the most potent compounds in this respect. In addition, we have cross-compared yeast results with antibacterial and antitumor activities. We discuss the relationship between the mechanistic findings, the antiproliferative activities, and the physicochemical properties of the naphthoquinones.

Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.

Towards targeting anticancer drugs: Ruthenium(II)-arene complexes with biologically active naphthoquinone-derived ligand systems

Anticancer active metal complexes with biologically active ligands have the potential to interact with more than one biological target, which could help to overcome acquired and/or intrinsic resistance of tumors to small molecule drugs. In this paper we present the preparation of 2-hydroxy-[1,4]-naphthoquinone-derived ligands and their coordination to a RuII(η6-p-cymene)Cl moiety. The synthesis of oxime derivatives resulted in the surprising formation of nitroso-naphthalene complexes, as confirmed by X-ray diffraction analysis. The compounds were shown to be stable in aqueous solution but reacted with glutathione and ascorbic acid rather than undergoing reduction. One-electron reduction with pulse radiolysis revealed different behavior for the naphthoquinone and nitroso-naphthalene complexes, which was also observed in in vitro anticancer assays.

Synthesis and evaluation of (±)-dunnione and its ortho-quinone analogues as substrates for NAD(P)H:quinone oxidoreductase 1 (NQO1)

Natural product (±)-dunnione (2) and its ortho-quinone analogues (3-8) were synthesized and found to be substrates for NQO1. The structure-activity relationship study revealed that the biological activity was favored by the presence of methyl group at the C ring and methoxy group at the A ring. The docking studies supported the rationalization of the metabolic studies. Deeper location in the active site of NQO1, interactions with hydrophobic pocket and C-H...π interactions with the adjacent Phe178 residue contributed to the better catalytic efficiency and specificity to NQO1. Cytotoxicity studies and determination of superoxide (O2-) production in the presence and absence of the NOQ1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling.