- Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations
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We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 2–C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.
- Carneiro, José Walkimar M.,Costa, Pedro Mikael S.,Filho, Eclair Venturini,Fiorot, Rodolfo G.,Gomes, Anne Caroline C.,Greco, Sandro J.,Guimar?es, Celina J.,Lemos, Bárbara C.,Pessoa, Claudia,Westphal, Regina,de Oliveira, Fátima C. E.
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- Palladium catalyzed Carbon–Hydrogen bond activation on amino-substituted quinones under acidic condition
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In this study, 2-(benzylamino)naphthalene-1,4-dione (4a) was used as the starting material to carry out a one-pot catalytic reaction in acetic acid with divalent palladium metal Pd(OAc)2 in a nitrogen atmosphere. Two compounds, 5a and 6a, were observed unexpectedly. Both compounds were characterized by spectroscopic methods as well as X-ray single crystal determination. The crystal structure of 5a reveals that a nitrogen-containing six-membered ring is formed; while the crystal structure of 6a shows that both oxazole and pyridine ring are generated. The optimized condition for making 6a was pursued. Derivatives of 4a, such as 4b and 4c, were also used as starting materials to proceed under the aforementioned optimal reaction conditions. Although the yields are not satisfactory, obviously the same patterns of corresponding compounds can be synthesized. The reaction of a 4a-structural related compound 9 under similar condition, two unexpected oxazole-containing compounds, 10 and 11, were obtained. The diverse pathways for this type of reactions even starting with slightly different substituents on the quinone indeed provides chemists with a perpetual motivation for further studies.
- Huang, Peng-Hao,Hong, Rui-Yu,Hong, Fung-E
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p. 2337 - 2347
(2021/10/08)
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- IDO inhibitor, preparation method and applications thereof
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The invention relates to an IDO inhibitor, a preparation method and applications thereof, and belongs to the technical field of medicinal chemistry. The IDO inhibitor with the characteristics of a structure represented by a general formula I or the pharma
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Paragraph 0155-0158; 0317-0320
(2020/04/17)
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- Antibacterial Activity of 2-Amino-1,4-naphthoquinone Derivatives against Gram-Positive and Gram-Negative Bacterial Strains and Their Interaction with Human Serum Albumin
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A series of 2-amino-1,4-naphthoquinone derivatives (NQA-NQF) was synthesized by alternative methods (ultrasonication and microwave irradiation), with yields ranging from 40 to 71%, and without the need of further recrystallization. Each compound was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus) and five Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae positive β-lactamase) bacteria strains. The NQF was the most active amino-naphthoquinone derivative with minimum inhibitory concentration (MIC) of 31.2 μg mL-1 against K. pneumoniae positive β-lactamase (a common intestinal bacteria which can cause life-threatening infections). On the other hand, NQA and NQC showed good activity as a potential antibiotic for the bacteria strains assayed, except for K. pneumoniae. In addition, the affinity of these three most active compounds (NQA, NQC, and NQF) for human serum albumin (HSA) was evaluated employing multiple spectroscopic techniques (steady-state, time-resolved, and synchronous fluorescence, as well as circular dichroism), combined with theoretical calculations (molecular docking). The interaction HSA:2-amino-1,4-naphthoquinones occurs spontaneously and moderately inside the subdomain IIA (Sudlow’s site I) via hydrogen bonding and van der Waals forces.
- Chaves, Otávio A.,Echevarria, Aurea,Netto-Ferreira, José Carlos,Paiva, Rojane O.,da Costa, Gisela L.,da Silva, Carla C.
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p. 1838 - 1851
(2020/10/09)
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- Identification of unusual C-Cl...π contacts in 2-(alkylamino)-3-chloro-1,4-naphthoquinones: Effect of N-substituents on crystal packing, fluorescence, redox and anti-microbial properties
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The chemo-selective reaction of 2,3-dichloro-1,4-naphthoquinone with different primary amines affords access to a series of derivatives, such as 2-(alkylamino)-3-chloro-1,4-naphthoquinone (1-6) and 2-(benzylamino)-1,4-naphthoquinone (7), in good yields. All the compounds 1-7 were characterized thoroughly by microanalysis, standard spectroscopy and thermogravimetric methods. The supramolecular structures of 1-4 and 7 were studied by means of single-crystal X-ray diffraction to gauge the influence of substituents that are present on the amine functionality on the association of molecules in the solid state. The study showed that the introduction of various amine N-substituents induces conformational changes that apparently modify the nature and number of donor-acceptor sites for noncovalent interactions, leading to diverse crystal packing patterns. Interestingly, the introduction of 2-(benzylamino)- and 2-(2-pyridylmethylamino)- substituents in 2 and 4 successfully switched on the C-Cl...π synthon, which is scarcely seen in the crystal packing of organic molecules. Compounds 1, 2, 4 and 5 fluoresced in the range of 350-620 nm with concomitant Stokes shifts of 81, 131, 141 and 131 nm, respectively, and their cyclic voltammograms evidenced two quasi-reversible single-electron waves. All the compounds (except 5) exhibited their first endothermic peak on the DTA curves without any mass loss due to the phase change, attributable to the melting points of the respective compounds. Remarkably, compound 5 exhibited an enhanced antibacterial activity against S. aureus and proved to be a more potent antibacterial agent than the well-known drug "ciprofloxacin".
- Singh, Vinay K.,Verma, Sanjay K.,Kadu, Rahul,Mobin, Shaikh M.
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p. 43669 - 43686
(2015/05/27)
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- Divergent and facile Lewis acid-mediated synthesis of N-alkyl 2-aminomethylene-1,3-indanediones and 2-alkylamino-1,4-naphthoquinones
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N-Alkyl 2-aminomethylene-1,3-indanediones and 2-alkylamino-1,4-naphthoquinones are known for their diverse and versatile bioactivities and applications. Traditionally, these two compounds were synthesized in separate routes using different materials. By e
- Zhang, Qian,Chang, Cheng-Wei Tom
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supporting information
p. 893 - 896
(2015/02/05)
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- Activity analysis and preliminary inducer screening of the chicken DAZL gene promoter
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This study was aimed at identifying the active control area of chicken DAZL gene core promoter, to screen optimum inducers of the DAZL gene, thus to enhance the differentiation of embryonic stem cells into spermatogonial stem cells. Fragments of chicken DAZL gene promoter were cloned into fluorescent reporter plasmids and transfected into DF-1 cells. Then Dual-Luciferase Reporter Assay System was used to identify the activity of the DAZL gene under different inducers. Our studies showed that the DAZL core promoter region for the Suqin yellow chicken was 383 to 39 bp. The dual-luciferase reporter showed that all-trans retinoic acid (ATRA), a retinoic acid receptor alpha agonist (tamibarotene/Am80), or estradiol (E2) could significantly enhance DAZL transcription. The in vitro inductive culture of chicken ESCs demonstrated that, with ATRA treatment, DAZL transcription peaked at 6 days and then decreased slowly; whereas, DAZL transcription was continuous and peaked at 10 days with Am80 treatment. E E2 treatment significantly increased DAZL expression after 8 days. All three treatments were associated with the appearance of male germ cell (MGC)-like cells on day 10. These results provide the optimum inducer screening of the DAZL gene and lay the foundation for further screening of compounds that can induce the differentiation of ESCs into MGCs in vitro.
- Zhang, Lei,Zhu, Rui,Zuo, Qisheng,Li, Dong,Lian, Chao,Tang, Beibei,Xiao, Tianrong,Zhang, Yani,Li, Bichun
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p. 6595 - 6605
(2015/04/14)
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- INHIBITORS OF THE MITF MOLECULAR PATHWAY
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Provided herein are compounds of the formula (IV) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful as MITF inhibitors, MITF pathway inhibitors and for the treatment of cancer.
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Paragraph 00369
(2015/01/09)
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- Development of quinone analogues as dynamin GTPase inhibitors
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Virtual screening of the ChemDiversity and ChemBridge compound databases against dynamin I (dynI) GTPase activity identified 2,5-bis-(benzylamino)-1,4- benzoquinone 1 as a 273 ± 106 μM inhibitor. In silico lead optimization and focused library-led synthesis resulted in the development of four discrete benzoquinone/naphthoquinone based compound libraries comprising 54 compounds in total. Sixteen analogues were more potent than lead 1, with 2,5-bis-(4-hydroxyanilino)-1,4-benzoquinone (45) and 2,5-bis(4-carboxyanilino)- 1,4-benzoquinone (49) the most active with IC50 values of 11.1 ± 3.6 and 10.6 ± 1.6 μM respectively. Molecular modelling suggested a number of hydrogen bonding and hydrophobic interactions were involved in stabilization of 49 within the dynI GTP binding site. Six of the most active inhibitors were evaluated for potential inhibition of clathrin-mediated endocytosis (CME). Quinone 45 was the most effective CME inhibitor with an IC50(CME) of 36 ± 16 μM.
- Macgregor, Kylie A.,Abdel-Hamid, Mohammed K.,Odell, Luke R.,Chau, Ngoc,Whiting, Ainslie,Robinson, Phillip J.,McCluskey, Adam
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p. 191 - 206
(2014/08/18)
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- COMPOSITIONS AND METHODS FOR TREATING NEUROLOGICAL DISEASES OR INJURY
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Provided are compounds for the treatment of neurological diseases or injuries, including neurodegenerative diseases, stroke, trauma, epilepsy, acute and chronic kidney injuries, diabetes mellitus, and/or seizures. In some embodiments, derivatives of vitamin K are provided.
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Paragraph 00219
(2014/05/24)
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- Bifunctionalisation of 1,4-naphthoquinone by the oxidative addition of an alkylamine and iodine
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Novel 2-iodo-3-(alkylamino) naphthalene-1,4-diones are formed in 33-70% yield by the reaction of alkylamine and 1, 4-naphthoquinone in the presence of iodine.
- Huang, Huan-Ming,Li, Yu-Jin,Dai, Yin-Ping,Yu, Wu-Bin,Ye, Qin,Gao, Jian-Rong
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- Synthesis, antibacterial and antifungal activity of 2-amino-1,4- naphthoquinones using silica-supported perchloric acid (HClO4- SiO2) as a mild, recyclable and highly efficient heterogeneous catalyst
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Perchloric acid adsorbed on silica gel (1 mol%) has been found to be an efficient and recyclable heterogeneous catalyst for rapid conjugate addition of primary and secondary amines with 1,4-naphthoquinone to afford 2-amino-1,4-naphthoquinones under ultrasonication in moderate to high yields without using any solvent. The compounds tested for in vitro antimicrobial activity have shown high antibacterial activity against Gram positive bacteria Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus as compared to Gram negative bacteria Burkholderia cepacia, Escherichia coli, Enterobacter cloacae, Klebseilla pneumoniae and Pseudomonas aeruginosa. High antifungal activity has been observed against Candida albicans and Issatchenkia orientalis for all the compounds.
- Sharma, Upendra,Katoch, Deepali,Sood, Swati,Kumar, Neeraj,Singh, Bikram,Thakur, Archana,Gulati, Arvind
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p. 1431 - 1440
(2014/01/06)
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- Structure-activity relationship study of vitamin K derivatives yields highly potent neuroprotective agents
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Historically known for its role in blood coagulation and bone formation, vitamin K (VK) has begun to emerge as an important nutrient for brain function. While VK involvement in the brain has not been fully explored, it is well-known that oxidative stress plays a critical role in neurodegenerative diseases. It was recently reported that VK protects neurons and oligodendrocytes from oxidative injury and rescues Drosophila from mitochondrial defects associated with Parkinson's disease. In this study, we take a chemical approach to define the optimal and minimum pharmacophore responsible for the neuroprotective effects of VK. In doing so, we have developed a series of potent VK analogues with favorable drug characteristics that provide full protection at nanomolar concentrations in a well-defined model of neuronal oxidative stress. Additionally, we have characterized key cellular responses and biomarkers consistent with the compounds' ability to rescue cells from oxidative stress induced cell death.
- Josey, Benjamin J.,Inks, Elizabeth S.,Wen, Xuejun,Chou, C. James
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p. 1007 - 1022
(2013/03/28)
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- C-H functionalization of 1,4-naphthoquinone by oxidative coupling with anilines in the presence of a catalytic quantity of copper(II) acetate
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The oxidative addition of anilines (2) with 1,4-naphthoquinone (3) to give N-aryl-2-amino-1,4-naphthoquinones (1) was found to be catalyzed by copper(II) acetate. In the absence of the catalyst, the reactions are slower and give lower yields with the formation of many colateral products. In the presence of 10 mol % hydrated copper(II) acetate, the reactions are generally more efficient in that they are cleaner, higher yielding, and faster.
- Lisboa, Cinthia Da S.,Santos, Vanessa G.,Vaz, Boniek G.,De Lucas, Nanci C.,Eberlin, Marcos N.,Garden, Simon J.
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supporting information; experimental part
p. 5264 - 5273
(2011/08/04)
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- Gold(III)-catalyzed 1,4-nucleophilic addition: Facile approach to prepare 2-amino-1,4-naphthalenedione and 6-amino-5,8-quinolinedione derivatives
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An efficient approach is developed to prepare different 2-amino-1,4-naphthalenedione and 6-amino-5,8-quinolinedione derivatives regioselectively by Au(III)-catalyzed 1,4-nucleophilic addition and subsequent oxidation. A wide variety of primary, secondary, and aromatic amines, as well as allylamine and 2-butynylamine are well tolerated under the mild conditions to give products in moderate to good yields. Georg Thieme Verlag Stuttgart.
- Jiang, Chunhui,Wang, Shaozhong
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experimental part
p. 1099 - 1102
(2009/10/14)
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- Facile synthesis of 2-amino-1,4-naphthoquinones catalyzed by molecular iodine under ultrasonic irradiation
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The conjugate addition reactions of amines with 1,4-naphthoquinone were catalyzed efficiently by molecular iodine under ultrasonic irradiation to afford 2-amino-1,4-naphthoquinones in moderate to excellent yields. Copyright Taylor & Francis Group, LLC.
- Liu, Bing,Ji, Shun-Jun
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p. 1201 - 1211
(2008/09/18)
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- Synthesis of CBI-PDE-I Dimer, the Benzannelated Analogue of CC-1065
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A practical synthesis of CBI (2), utilizing inexpensive starting materials, was developed and applied to the synthesis of benzannelated analogs of CC-1065, in particular CBI-PDE-I-dimer (13) and CBI-bis-indole (17).While a Sharpless asymmetric dihydroxylation reaction proved effective at providing optically active intermediates, a more classical resolution procedure was used to prepare materials of higher optical purity.A novel cyclization employing a six-membered-ring intermediate (12) was employed to construct the cyclopropyl ring in CBI.Like CC-1065, CBI-PDE-I-dimer appears to cause delayed toxicity in mice.
- Aristoff, Paul A.,Johnson, Paul D.
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p. 6234 - 6239
(2007/10/02)
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- Independent Synthesis of the Violet Dyes and of a By-product Formed in the Reaction of 1,2-Naphthoquinone-4-sulfonic Acid with Primary Aliphatic Amines
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4-Dimethylamino-1,2-naphthoquinone (8) and 2-dimethylamino-1,4-naphthoquinone (10) are O-methylated by methyl fluorosulfonate to form the stable iminium salts 9 and 11.In analogous way the 2-alkylamino-1,4-naphthoquinones 13 were transformed into the iminium salts 14.These salts condense with 3-amino-4-hydroxynaphthalene-1-sulfonic acid (15) to give the violet 3--4-hydroxynaphthalene-1-sulfonic acids 2.The iminium salt 14c reacts with benzylamine to yield the vinylogous amidinium salt 19, which is oxidised by silver oxide inpyridine to give the N-benzylidene-2-phenyl-5-naphthoxazolamine 20.Reduction of 20 with LiAlH4 leads to the formation of N-benzyl-2-phenyl-5-naphthoxazolamine (7).
- Lohmann, Ulrike,Hartke, Klaus
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p. 313 - 323
(2007/10/02)
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