Aminonaphthoquinone Derivatives Research Articles

New Amino Naphthoquinone Derivatives as Anti-Trypanosoma cruzi Agents Targeting Trypanothione Reductase.

To develop novel chemotherapeutic alternatives for the treatment of Chagas disease, in this study, a set of new amino naphthoquinone derivatives were synthesised and evaluated in vitro on the epimastigote and trypomastigote forms of Trypanosoma cruzi strains (NINOA and INC-5) and on J774 murine macrophages. The design of the new naphthoquinone derivatives considered the incorporation of nitrogenous fragments with different substitution patterns present in compounds with activity on T. cruzi, and, thus, 19 compounds were synthesised in a simple manner. Compounds 2e and 7j showed the lowest IC50 values (0.43 µM against both strains for 2e and 0.19 µM and 0.92 µM for 7j). Likewise, 7j was more potent than the reference drug, benznidazole, and was more selective on epimastigotes. To postulate a possible mechanism of action, molecular docking studies were performed on T. cruzi trypanothione reductase (TcTR), specifically at a site in the dimer interface, which is a binding site for this type of naphthoquinone. Interestingly, 7j was one of the compounds that showed the best interaction profile on the enzyme; therefore, 7j was evaluated on TR, which behaved as a non-competitive inhibitor. Finally, 7j was predicted to have a good pharmacokinetic profile for oral administration. Thus, the naphthoquinone nucleus should be considered in the search for new trypanocidal agents based on our hit 7j.

Design, synthesis, and catalytic performance of modified graphene oxide based on a cobalt complex as a heterogenous catalyst for the preparation of aminonaphthoquinone derivatives.

We are reporting a functionalized graphene oxide catalyst developed by modifying graphene oxide surface using the covalent attachment of an amino-functionalized SiO2 sphere/cobalt complex. Silica network has special characteristics including mechanical strength, high thermal and chemical stability with good dispersion in solvents. The silica/graphene oxide mixture provides improved properties and extends the scope of application. Graphene oxide was functionalized by spherical silica with the help of hybrid silane-containing nitrogen to coordinate with Co(ii) for increasing the catalytic activity. The catalyst was characterized by Fourier Transform Infrared (FT-IR) spectroscopy, powder X-ray diffraction (XRD), Energy Dispersive X-ray (EDX), Scanning Electron Microscopy (SEM), Raman spectroscopy, and Thermal Gravimetric (TGA) analyses. The catalyst showed high catalytic activity for multi-component reactions in the synthesis of aminonaphthoquinones in ethanol solvent. The catalyst's ability to improve the yield (96–98%), reduce the reaction time (5–8 min), and recycling ability are important benefits for the catalyst.

Solvent and catalyst-free synthesis of some new aminonaphthoquinones from lawsone, ninhydrin and heteroaryl amines

An efficient and easy method has been developed for the preparation of some new aminonaphthoquinone derivatives from a one-pot three-component condensation of 2-hydroxy-1,4-naphthoquinone, ninhydrin and heteroaryl amines under catalyst and solvent-free conditions at 75 °C. The protocol describes in situ generated imine as intermediate from the condensation reaction of ninhydrin with heteroaryl amines followed by the addition of 2-hydroxynaphthalene-1,4-dione to the imine, afforded the desired products. The operational simplicity of the procedure, shorter reaction times, simple workup procedure, clean reaction, easy purification of products by nonchromatographic methods, environmentally friendly conditions and high yields make this method much attractive.

Oxidative transformation of 1-naphthylamine in water mediated by different environmental black carbons

Black carbons (BCs) are ubiquitous in the natural environment and can significantly influence the environmental behavior of pollutants. This work examined the mediating effects of graphite, soot, and biochar on 1-naphthylamine (1-NA) oxidation under aerobic conditions. It was shown that the three BCs significantly promoted the oxidation of 1-NA in the dark, and the mediation efficiency of graphite was much greater than that of soot or biochar. The oxidation products were the coupling oligomers (dimers and trimers) and the oxygen-containing oligomers of 1-NA (di-OH-1-NA, OH-azo naphthalene, OH-trimers and amino-naphthoquinone derivatives etc.). The phenolic OH on BCs were identified as the active sites for 1-NA oxidation, which could stimulate O2 to produce reactive oxygen species through successive single electron transfer and then cause 1-NA oxidation. Moreover, the superior catalytic performance of graphite was also related to its high electrical conductivity. The synergies between the sp2-hybridized carbon surface and the active sites (such as phenolic OH and defects) facilitated the oxidation of 1-NA on graphite. Findings in this study not only are helpful for better understanding the reactivity of environmental BCs, but also provide new insights into the risk assessment of 1-NA in the natural environment.

In Vitro Analysis of the Combinatory Effects of Novel Aminonaphthoquinone Derivatives and Curcumin on Breast Cancer Progression.

We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.

Montmorillonite K-10 catalyzed Mannich reaction: Synthesis of aminonaphthoquinone derivatives from Lawsone

An efficient one-pot protocol for the synthesis of 2-((substituted amino)(4-phenyl)methyl)-3-hydroxy-naphthalene-1,4-dione derivatives has been developed by the three-component reaction of 2-hydroxy-naphthalene-1,4-dione, aromatic aldehydes and anilines/heterocyclic amines using montmorillonite K-10 as a catalyst. The advantages of this method include short reaction time, excellent yield and easy work-up.

One pot synthesis of aminonaphthoquinone derivatives using Cu(II) immobilized on hyperbranched polyglycerol functionalized graphene oxide as a reusable catalyst under solvent-free conditions

A new Cu(II) immobilized on hyperbranched polyglycerol (HPG) functionalized graphene oxide catalyst was prepared and characterized by FT-IR, TGA, FE-SEM, XRD, and ICP-OES techniques. This catalyst was used efficiently for the preparation of aminonaphthoquinones via one-pot three-component condensation reaction under solvent-free conditions. The catalyst could be easily recovered and reusable several times without a significant loss of activity, which make this method attractive and in a close agreement with green chemistry.

Evaluation of the Effects of Aminonaphthoquinone Derivatives in Combination with Curcumin Against ER-positive Breast Cancer and Related Tumours.

Combination therapies are often explored to treat cancer. The use of curcumin as an adjuvant to current chemotherapies has been reported, whilst aminonaphthoquinones have shown potential as anticancer agents in various tumour cell lines. This study aimed at screening synthetic aminonathoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) alone and in combination with curcumin for anti-breast cancer activity. Combination effects were determined in MCF-7 breast cancer cells using combination index analyses. Synergistic anti-proliferative effects were further investigated in breast (MCF-7, MDA-MB-231), osteosarcoma (MG-63) and endometrial (HEC-1A) cancer-derived cells. Rau 015 (15 μM) and curcumin (112.5 μM) significantly reduced MCF-7, MDA-MB-231 and MG-63 cell proliferation compared to individual treatment, indicating synergistic anti-proliferative effects. Rau 018 (30 μM) and curcumin (100 μM) displayed similar effects in MCF-7 and MG-63 cells. We report on the potential of Rau 015 or Rau 018 as anti-breast cancer agents when combined with curcumin.

Synthesis, Computational Study, and Evaluation of In Vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives

Synthesis, Computational Study, and Evaluation of In Vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives

Synthesis, Computational Study, and Evaluation of in vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives

Synthesis, Computational Study, and Evaluation of in vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives

Probing the ESIPT process in 2-amino-1,4-naphthoquinone: thermodynamics properties, solvent effect and chemometric analysis

The developing of fluorescent probes for disease diagnosis is a very important task, which favors precision in the diagnosis and success in the treatment. Recently, amino-naphthoquinone derivatives showed to be efficient fluorescent probes for disease diagnosis. Those compounds exhibit excited-state intramolecular proton transfer (ESIPT), which is the main mechanism responsible for their use as fluorescent probes. The understanding of the ESIPT mechanism for naphthoquinones is an important way of developing more efficient and selective fluorescent probes. In this work, the ESIPT process for ANQ was performed at the TD-DFT/CAM-B3LYP/DGTZVP and DFT/B3LYP/DGTZVP level for the electronic and geometric studies. These parameters were selected for the PCA analysis. The solvent effect was investigated by using PCM and IEF-PCM in chloroform, water and methanol. 2-Amino-1,4-naphthoquinone (ANQ) showed blue emission for fluorescence, having keto–keto* absorption at 4.50 eV and the enol–enol* decay at 2.75 eV. The solvent effect was evaluated, and the ESIPT process of ANQ was favorable in nonpolar and polar solvents. Furthermore, the thermodynamics properties showed that the ESIPT is favorable with a proton transfer equilibrium constant of ~105.

Synthesis and characterization of Bi(iii) immobilized on triazine dendrimer-stabilized magnetic nanoparticles: a reusable catalyst for the synthesis of aminonaphthoquinones and bis-aminonaphthoquinones

A novel method for synthesis of aminonaphthoquinone derivatives using Fe3O4@TDSN–Bi(iii) is reported.

Synthesis of novel aminoquinonoid analogues of diospyrin and evaluation of their inhibitory activity against murine and human cancer cells

The synthesis and tumor-inhibitory activity of a series of aminonaphthoquinone derivatives of diospyrin, which was isolated from Diospyros montana Roxb., are presented here for the first time. An aminoacetate derivative showed the maximum (∼93%) increase in life span in vivo against murine Ehrlich ascites carcinoma (EAC) at a dose of 1 mg kg −1 day −1 (ip; five doses), and the lowest IC 50 (0.06 μM) in vitro. Further, the same analogue also exhibited considerable enhancement in antiproliferative activity when evaluated against human cell lines, viz. malignant skin melanoma and epidermoid laryngeal carcinoma (IC 50 = 0.06 and 0.92 μM, respectively) in comparison to the natural precursor, diospyrin (IC 50 = 0.82 and 3.58 μM, respectively). Moreover, diospyrin and all its derivatives were found to show significantly greater (∼17- to 1441-fold) cytotoxicity against the tumor cells as compared to normal human lymphocytes. All these quinonoids generated substantial amounts of reactive oxygen species in EAC cells, more or less commensurate to their respective IC 50 values.

Novel human hair dyes II Synthesis and structure determination of leuco-mono aminonaphthoquinone derivatives based on naphthazarin.

Novel compounds related to leuco-monoaminonaphthoquinones derived from naphthazarin were synthesized. These leuco-compounds were stable even in aerated solvents. Their structures in tautomeric isomers were definitely elucidated by 1H, 13C-NMR spectroscopies. The assignment of 13C-NMR was achieved by 1H, 13C long range selective proton decoupling (LSPD) method. The structure of leuco-compound of naphthazarin was confirmed to be 2, 3-dihydro-5, 8-dihydroxynaphthalene-1, 4-dione. The structures of leuco-compounds of 2-butylaminonaphthazarin and 5-butylamino-8-hydroxynaphthoquinone were revealed to be 6-butylamino-2, 3-dihydro-5, 8-dihydroxynaphthalene-1, 4-dione and 5-butylamino-2, 3-dihydro-8-hydroxynaphthalene-1, 4-dione, respectively.

Reaction of 2-Amino-1,4-Naphthoquinone Derivatives with Dimethyl Acetylenedicarboxylate

Abstract The chemistry of quinone has been extensively studied since the turn of the century1. The major thrust of the work has been biologically oriented due to the activity of this class of compound toward several microorganisms2. In the naphthoquinone series, where the hydroxy-quinones are represented by 2-hydroxy-1,4-naphthoquinones, there are references to bactericidal3 and fungicidal4 activity. Aminonaphthoquinone derivatives are less studied but there are several reports in the literature indicating their activity against pneumococcus5, Eschericia Coli 6, oral bacteria7 and Plasmodium berghei8. Aminonaphthoquinone compounds have been found to be more potent inhibitors of D.N.A. synthesis than mitomycin in Ehrlich ascites carcinoma cells9–11.