Laccase-Catalyzed Synthesis of 1,4-Naphthoquinone Sulfides and 1,4-Naphthoquinone Sulfide Dimers (original) (raw)
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Synthesis and Structural Analysis of Some New Sulfanyl Amino 1,4-Naphthoquinone Derivatives
Journal of the Turkish Chemical Society, Section A: Chemistry, 2017
In this study, some new sulfanyl-substituted amino 1,4-naphthoquinone derivatives which possess two electron-donating groups in the amino fragment were synthesized and their structures were analyzed by spectroscopic techniques. First, 2-chloro-3-[(2,4dimethoxyphenyl)amino]naphthalene-1,4-dione (3a) and 2-chloro-3-[(3,5dimethoxyphenyl)amino]naphthalene-1,4-dione (3b) were obtained from the reactions of dichloro-1,4-naphthoquinone (1) with 2,4-dimethoxyaniline and 3,5-dimethoxyaniline. In the following step, the compounds 3a,b were reacted with aliphatic nucleophiles; ethyl-, 1-propyl-, and 1-pentyl mercaptan. S-nucleophiles attacked the carbon atom of 1,4-naphthoquinone core and displaced the chlorine atom to create target molecules; 2-arylamino-3-(ethylthio)naphthalene-1,4-dione (5a,b), 2-arylamino-3-(propylthio)naphthalene-1,4-dione (5c,d), 2-arylamino-3-(pentylthio)naphthalene-1,4-dione (5e,f) derivatives. The structures of the synthesized compounds were elucidated by utilizing 1D and 2D NMR techniques with additional spectroscopic data (mass and FTIR).
Investigational New Drugs, 2019
We have previously reported on the synthesis of 1,4-naphthoquinone-sulfides and in this investigation we report on their anticancer activity against 6 human cancer cell lines to evaluate their cytostatic effects. The 1,4-naphthoquinone-2,3-bis-sulfides were most effective against melanoma (UACC62) (GI 50 = 6.5-10 μM) and prostate (PC3) (GI 50 = 5.51-8.53 μM) cancer cell lines. They exhibited better cytostatic effects than etoposide (GI 50 = 0.56-36.62 μM), parthenolide (GI 50 = 3.58-25.97 μM) and VK3 (GI 50 = 3.41-22.59 μM) against several of the cancer cell lines. These compounds are generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI-38). One compound produces ROS which results in breast (MCF7) cancer cell death caused by apoptosis as evidenced by caspase 3/7 activation. Apoptosis was found to occur by a mitochondrial pathway and not by cell cycle arrest. Gene expression studies showed that p53 (a tumour suppressor), Mdm-2 (a p53 regulator) and Bcl-2 (apoptosis inhibitor) were up-regulated during apoptosis induction. These results encourage further research for potential application in cancer chemotherapy.
European Journal of Medicinal Chemistry, 2011
A series of novel N 9-heterobivalent b-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC 50 value of lower than 20 lM. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 5b and 5w exhibited that tumour inhibition rate of over 40% in the Sarcoma 180 and Lewis lung cancer animal models. Preliminary structure-activity relationships (SARs) analysis indicated that: (1) C 1-methylation and C 7-methoxylation were favorable for increased activities; (2) 3-Pyridyl or 2-thienyl group substituent into position-1 of the b-carboline core, and the aryl substituent into another b-carboline ring might be detrimental to cytotoxic effects of this class compounds. Investigation of the preliminary mechanism of action demonstrated that compound 5b had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay.
Synthesis of 1,4-naphthoquinones derivatives under non-conventional conditions and in silico studies
Proceedings of 6th International Electronic Conference on Medicinal Chemistry, 2020
Microwave irradiation synthesis were completed within ≤ 10 min, whereas similar reactions under conventional heating at reflux gave lower or similar yields, with comparatively longer reaction times. For arylamines derivatives (4a-d and 5a-d) yields were significantly higher for 1,4-NQ derivatives (4a-d), due to the presence of CaCO 3. For alkylamines derivatives (4e-g and 5e-g) similar results were obtained with both precursors. Compounds were obtained by one-step Michael addition to C2 of nuclear naphthoquinone structure. Structural characterization were assigned based on their 1 H and 13 C NMR spectra and two-dimensional NMR (HSQC and HMBC) techniques. ESI-Mass spectrometry was used to corroborate NMR data and all compounds exhibited the expected m/z signals correspondent to the protonated molecules [M+H] + .
Investigation of the antibacterial and antifungal activity of thiolated naphthoquinones
Drug Development Research
The WHO has stated that antibiotic resistance is escalating to perilously high levels globally and that traditional therapies of antimicrobial drugs are futile against infections caused by resistant microorganisms. Novel antimicrobial drugs are therefore required. We report in this study on the inhibitory activity of the 1,4-naphthoquinone-2,3-bis-sulfides and 1,4naphthoquinone sulfides against two bacteria and a fungus to determine their antimicrobial properties. The 1,4-naphthoquinone sulfides have potent activity with a minimum inhibitory concentration (MIC) of 7.8 μg/mL against Staphylococcus aureus (Gram +ve), an MIC of 23.4 μg/mL against the fungus, Candida albicans, which was better than that of Amphotericin B (MIC = 31.3 μg/mL), and against Escherichia coli (Gram −ve) an MIC of 31.3 μg/mL was obtained. The 1,4-naphthoquinone had an MIC of 11.7 μg/mL against S. aureus and the 1,4-naphthohydroquinone also had the same activity against E. coli.
A General and Facile One-Pot Synthesis of Napthoquinone-1,3-dithioles in Aqueous Medium
Chemical Science Transactions, 2015
A general and facile one pot protocol for the preparation of napthoquinone-1,3-dithioles has been developed from the three-component reaction of primary amine, carbon disulfide and 2,3-dichloro-1,4-napthoquinone under aqueous conditions. Both aliphatic and aromatic primary amines were used to get the corresponding products in moderate to excellent yields. Moreover, this method is advantageous over reported methods.
Advanced Synthesis & Catalysis, 2020
An efficient and environmentally benign biocatalytic strategy for the synthesis of substituted 4arylamino-1,2-naphthoquinones was developed, through a cross-coupling reaction in which the 1,2naphthoquinone nucleus, formed in the biocatalytic process mediated by CotA-laccase from Bacillus subtilis, is the key synthetic intermediate. Electrochemical data and kinetic parameters were determined revealing a significant higher specificity of CotA-laccase for 4-amino-3-hydroxynaphthalene-1-sulfonic acid (AHNSA). This ability of CotA-laccase to discriminate between oxidisable aromatic amines allows the setup of one-pot reactions in the presence of the enzyme, between AHNSA and a set of appropriate aromatic amines under mild reaction conditions.