- Synthesis, characterization, computational and biological study of novel azabenzo[a]phenothiazine and azabenzo[b]phenoxazine heterocycles as potential antibiotic agent
-
Two angular phenothiazines and one angular phenoxazine were successfully synthesized via anhydrous base condensation reaction of 2,6-diamino-4-chloropyrimidine-5-thiol, with 7-chloro-5,8-quinolinequinone,2-aminothiophenol and 2-aminophenol, respectively. Condensation reaction between 2-6-diamino-4-chloropyrimidine-5-thiol and 7-chloro-5,8-quinolinequinone in the presence of anhydrous sodium carbonate yielded 10-amino-8-chloro-1,9,11-triaza-5H-benze[a]phenothiazine-5-one, 1-aza-5H-benzo[a]phenothiazine-5-one and 1-aza-5H-benzo[a]phenoxazine-5-one were produced with anhydrous basic condensation between 7-chloro-5,8-quinolinequinone and 2-aminothiophenol and 2-aminophenol respectively. These angular azaphenothiazin-5-ones and angular azaphenoxazine-5-one were converted to their derivatives via palladium(o)/piperazine ligand utilizing Mizoroki–Heck cross coupling tandem reaction to obtain six derivatized compounds. The synthesized compounds are intensely coloured and their structural elucidation were established by combined spectroscopic and elemental analytical data. In silico and in vitro screening methods were used to investigate the antibacterial potencies of the compounds. All the compounds, except one, interacted with Type I SPase, an unconventional validated antibiotic enzyme targeted in combating antibacterial resistant, at low micromolar range. They also showed activity against the tested bacteria: Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa. In fact, B. cereus exhibited more susceptibility towards four of the compounds than the standard drug—ciprofloxacin. The predicted binding modes of four compounds with outstanding activities were finally studied to identify vital ligand–protein interactions, which can serve as template during activity optimization process.
- Ibeanu, Fidelia N.,Onoabedje, Efeturi A.,Ibezim, Akachukwu,Okoro, Uchechukwu C.
-
-
Read Online
- Powder diffraction study of the hydrogen bonds in nitroxoline and its hydrochloride.
-
The crystal structures of 8-hydroxy-5-nitroquinoline, C9H6N2O3, (I), and 8-hydroxy-5-nitroquinolinium chloride, C9H7N2O3+*Cl-, (II), have been determined from X-ray powder data. In (I), the molecules are linked via moderately strong hydrogen bonds to form dimers. Such a packing motif is likely to be responsible for the low solubility of (I) in water. In (II), the inversion-related cations form stacks, and anions fill the interstack channels.
- Yatsenko,Paseshnichenko,Chernyshev,Schenk
-
-
Read Online
- Design, synthesis, and evaluation of multitarget-directed selenium-containing clioquinol derivatives for the treatment of Alzheimer's disease
-
A series of selenium-containing clioquinol derivatives were designed, synthesized, and evaluated as multifunctional anti-Alzheimer's disease (AD) agents. In vitro examination showed that several target compounds exhibited activities such as inhibition of metal-induced Aβ aggregation, antioxidative properties, hydrogen peroxide scavenging, and the prevention of copper redox cycling. A parallel artificial membrane permeation assay indicated that selenium-containing clioquinol derivatives possessed significant blood-brain barrier (BBB) permeability. Compound 8a, with a propynylselanyl group linked to the oxine, demonstrated higher hydrogen peroxide scavenging and intracellular antioxidant activity than clioquinol. Furthermore, 8a exhibited significant inhibition of Cu(II)-induced Aβ1-42 aggregation and was capable of disassembling the preformed Cu(II)-induced Aβ aggregates. Therefore, 8a is an excellent multifunctional promising compound for development of novel drugs for AD. (Chemical Equation Presented).
- Wang, Zhiren,Wang, Yali,Li, Wenrui,Mao, Fei,Sun, Yang,Huang, Ling,Li, Xingshu
-
-
Read Online
- Synthesis of 1-azabenzo[a]phenoxazin-5-one and 11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one and their Functionalized aryl derivatives via Mizoroki-Heck arylation methodology
-
The synthesis of angular 1-azabenzo[a]phenoxazin-5-one and 11-amino-1,8,10-triazabenzo[a] phenoxazin-5-one and their functionalized aryl derivatives via Mizoroki-Heck arylation methodology is reported. 11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one (16) and 1-azabenzo[a]phenoxazin-5-one (18) were synthesized by the reaction of 7-chloro-5,8-quinolinequinone (obtained by a multistage conversion of 8-hydroxyquinoline) with 4,5-diamino-6-hydroxypyrimidine and 2-aminophenol respectively in the presence of anhydrous sodium acetate. 11-Amino-1,8,10-triazabenzo[a]phenoxazin-5-one and 1-azabenzo[a]phenoxazin-5-one were subjected to Mizoroki-Heck coupling reaction by refluxing with iodobenzene derivatives, using 1,4-bis(diphenylphosphino)butane-palladium(11) chloride as catalyst, 1,4-bis-(2-hydroxy-3,5-ditertbutylbenzyl)piperazine as ligand and methanol as solvent at 60-650C for 4 h to afford in excellent yield aryl derivatives of angular 11-amino-1,8,10-triazabenzo[a]phenoxazin-5-one (19a-c) and 1-azabenzo[a]phenoxazin-5-one (20a-c) respectively. The structures were established by UV/visible, FTIR, proton-NMR and carbon-13 NMR spectral and elemental analysis.
- Oni, Timothy Toba,Okoro, Uchechukwu Chris,Ugwu, David Izuchukwu
-
-
Read Online
- Synthesis and anti-phytopathogenic activity of 8-hydroxyquinoline derivatives
-
Phytopathogenic fungi have become a serious threat to the quality of agricultural products, food security and human health globally, necessitating the need to discover new antifungal agents with de novo chemical scaffolds and high efficiency. A series of 8-hydroxyquinoline derivatives were designed and synthesized, and their antifungal activity was evaluated against five phytopathogenic fungi. In vitro assays revealed that most of the tested compounds remarkably impacted the five target fungi and their inhibitory activities were better than that of the positive control azoxystrobin. Compound 2, in particular, exhibited the highest potency among all the tested compounds, with an EC50 of 0.0021, 0.0016, 0.0124, 0.0059 and 0.0120 mM respectively against B. cinerea, S. sclerotiorum, F. graminearum, F. oxysporum and M. oryzae, followed by compound 5c. The morphological observations of optical microscopy and scanning electron microscopy revealed that compounds 2 and 5c caused mycelial abnormalities of S. sclerotiorum. Futhermore, the results of in vivo antifungal activity of compounds 2 and 5c against S. sclerotiorum showed that 5c possessed stronger protective and curative activity than that of 2, and the curative effects of 5c at 40 and 80 μg mL-1 (84.18% and 95.44%) were better than those of azoxystrobin (77.32% and 83.59%). Therefore, compounds 2 and 5c are expected to be novel lead structures for the development of new fungicides.
- Yin, Xiao-Dan,Sun, Yu,Lawoe, Raymond Kobla,Yang, Guan-Zhou,Liu, Ying-Qian,Shang, Xiao-Fei,Liu, Hua,Yang, Yu-Dong,Zhu, Jia-Kai,Huang, Xiao-Ling
-
p. 30087 - 30099
(2019/10/04)
-
- Study on Relationship Between Fluorescence Properties and Structure of Substituted 8-Hydroxyquinoline Zinc Complexes
-
Organic light-emitting diodes (OLEDs) produced from 8-hydroxyquinoline metal complexes play a vital role in modern electroluminescent devices. In this manuscript, a series of 8-hydroxyquinoline derivatives were synthesized by different methods and their corresponding zinc metal complexes were prepared. The UV and fluorescence properties of the complexes were measured aiming to understand the effect of substituents at the quinoline ring on the fluorescence properties of the complexes. When the C-5 of 8-hydroxyquinoline was replaced by halogen group, the fluorescence emission wavelengths had been red-shifted, at the same time, blue-shifted of fluorescence emission wavelength was observed when the C-5 position of 8-hydroxyquinoline was substituted by electron-withdrawing group. When the C-4 position of 8-hydroxyquinolie was substituted by methyl or the C-5 position was substituted by sulfonic acid group, the corresponding zinc complexes had higher fluorescence intensity than 8-hydroxyquinolie zinc.
- Jianbo, He,Tingting, Zhou,Yongjing, Cao,Yuanyuan, Zhang,Weiqing, Yang,Menglin, Ma
-
p. 1121 - 1126
(2018/08/17)
-
- Palladium catalyzed transformation and antimicrobial screening of novel angular azaphenothiazines
-
Base mediated condensation reaction between 2-amino-5-bromopyrazine-3[4H]-thione and 7-chloro-5,8-quinolinequinone under anhydrous condition gave 9-bromo-1,8,11-triaza-5H-benzo[a]phenothiazin-5-one. Palladium catalyzed cross-coupling reaction between 9-bromo-1,8,11-triaza-5H-benzo[a]phenothiazin-5-one and four arylated halogeno compounds utilizing Heck-Mizoroki protocol furnished 6-substituted derivatives of the angular tetracyclic heterocycle. Structures were assigned based on spectroscopic and elemental analytical data. Antimicrobial screening of these compounds showed they were biologically active.
- Godwin-Nwakwasi,Okoro,Ijeomah,Agbo,Ezeokonkwo
-
p. 742 - 748
(2017/02/10)
-
- New Aryl Derivatives of Quinolinedione and Related Heterocyclic Compounds
-
The synthesis of new derivatives of 6,7-dibromoquinoline-5,8-dione and 6,7-dichloroquinoline-5,8-dione via palladium/Sphos-mediated Suzuki–Miyaura cross-coupling reaction is reported. The 6,7-dibromoquinoline-5,8-dione and 6,7-dichloroquinoline-5,8-dione intermediates were prepared in a three-step reaction from 8-hydroxyquinoline. The palladium-catalyzed reactions of 6,7-dibromoquinoline-5,8-dione and 6,7-dichloroquinoline-5,8-dione with a variety of aryl boronic acids provide coupled compounds in high yields. The arylation of 6,7-dibromoquinoline-5,8-dione and 6,7-dichloroquinoline-5,8-dione with 4-bromophenyl boronic acid supplied 6,6′-(1,4-phenylene)bis(7-bromoquinoline-5,8-dione) and (4-(6-(4-(6-chloro-5,8-dihydroquinolin-7-yl)phenyl)-5,8-dihydroquinolin-7-yl)phenyl)boronic acid respectively, in addition to the expected coupled compounds in moderate yields. Also, Pd(0)/PPh3 allowed the 7-chloro-6-(4-nitrophenyl)quinoline-5,8-dione and 7-chloro-6-phenylquinoline-5,8-dione to be synthesized via Heck reaction. The yields of the synthesized target molecules depend largely on the reaction conditions and the type of ligands employed. Structural assignments of the synthesized compounds were established by spectra and analytical data.
- Egu, Samuel Attah,Okoro, Uchechukwu Chris,Onoabedje, Efeturi Abraham
-
p. 1572 - 1577
(2017/03/27)
-
- Design, synthesis and evaluation of clioquinol-ebselen hybrids as multi-target-directed ligands against Alzheimer's disease
-
A novel series of compounds obtained by fusing the metal-chelating agent clioquinol and the antioxidant ebselen were designed, synthesized and evaluated as multi-target-directed ligands against Alzheimer's disease (AD). Specifically, compared with their parent compounds clioquinol and ebselen, these hybrids demonstrated significant potency in inhibiting self- and Cu(ii)-induced amyloid-β (Aβ) aggregation and acted as remarkable antioxidants and biometal chelators. In addition, the hybrids showed considerable improvements in ebselen-related pharmacological properties, including the ability to mimic glutathione peroxidase and scavenge H2O2. Of these molecules, compound 10h was identified as a potential lead compound for AD therapy. Importantly, this compound was found to possess rapid H2O2 scavenging activity and glutathione peroxidase-like (GPx-like) activity. Moreover, compound 10h was able to efficiently disassemble preformed self- and Cu(ii)-induced Aβ aggregates. Furthermore, 10h was able to penetrate the central nervous system (CNS) and did not exhibit any acute toxicity in mice at doses up to 2000 mg kg-1.
- Wang, Zhiren,Li, Wenrui,Wang, Yali,Li, Xiruo,Huang, Ling,Li, Xingshu
-
p. 7139 - 7158
(2016/07/12)
-
- Computer-assisted designed "selenoxy-chinolin": A new catalytic mechanism of the GPx-like cycle and inhibition of metal-free and metal-associated Aβ aggregation
-
Using support from rational computer-assisted design, a novel series of hybrids (selenoxy-chinolin) designed by fusing the metal-chelating agent CQ and the antioxidant ebselen were synthesized and evaluated as multitarget-directed ligands. Most of the hybrids demonstrated significant ability to mimic GPx, which is highly consistent with the prediction results of DFT studies for the selenenyl sulfide intermediates in the computational design. Using 77Se, 1H and 13C NMR spectroscopy and high-resolution mass spectroscopy (HRMS), a novel catalytic mechanism, including a new selenium quinone active species, was first demonstrated. 2D NMR studies indicated that the typical hybrid has an effective interaction with Aβ. In addition, the optimal compound 12k was found to possess an excellent ability to scavenge peroxide and to inhibit self- and metal-induced Aβ aggregation, and an ability to disassemble preformed self- and metal-induced Aβ aggregates effectively. Furthermore, 12k was able to penetrate the central nervous system (CNS) and did not exhibit any acute toxicity in mice at doses up to 2000 mg kg-1. Overall, we demonstrated that hybrid 12k, through rational structure-based computational design, shows a potential for development as a therapeutic agent in AD.
- Wang, Zhiren,Wang, Yali,Li, Wenrui,Liu, Zhihong,Luo, Zonghua,Sun, Yang,Wu, Ruibo,Huang, Ling,Li, Xingshu
-
p. 20913 - 20925
(2015/12/11)
-
- Synthesis and anticonvulsant activity evaluation of 8-alkoxy-5-(4H-1,2,4- triazol-4-yl)quinoline derivatives
-
Two series of 8-alkoxy-5-(4H-1,2,4-triazol-4-yl)quinolines and 8-alkoxy-5-(2H-1,2,4-triazol-3-one-4-yl)quinolines were synthesized. The anticonvulsant activity of these compounds was evaluated with maximal electroshock seizure test and rotarod test. Among the synthesized compounds, 8-octoxy-5-(4H-1,2,4-triazol-4-yl)quinoline (4g) was the most active compound with ED50 of 8.80 mg/kg, TD50 of 176.03 mg/kg and protective index of 20.0. Its neurotoxicity was lower than all other synthesized compounds and also markedly lower than that of the reference drug carbamazepine. In addition, the potency of compound 4g against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline suggested its broad spectrum activity, and the mechanisms of action including inhibition of voltage-gated ion channels and modulation of GABAergic activity might involve in its anticonvulsant activity.
- Wang, Shi-Ben,Deng, Xian-Qing,Zheng, Yan,Zhang, Hong-Jian,Quan, Zhe-Shan
-
-
- Investigating the activity spectrum for Ring-Substituted 8-Hydroxyquinolines
-
In this study, a series of fourteen ring-substituted 8-hydroxyquinoline derivatives were prepared. The synthesis procedures are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity. They were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. Primary in vitro screening of the synthesized compounds was also performed against four mycobacterial strains and against eight fungal strains. Several compounds showed biological activity comparable with or higher than the standards isoniazid or fluconazole. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.
- Musiol, Robert,Jampilek, Josef,Nycz, Jacek E.,Pesko, Matus,Carroll, James,Kralova, Katarina,Vejsova, Marcela,O'Mahony, Jim,Coffey, Aidan,Mrozek, Anna,Polanski, Jaroslaw
-
scheme or table
p. 288 - 304
(2010/06/15)
-
- Technology of preparing 8-hydroxy-5-nitroquinoline
-
An efficient, two stage method is proposed for the preparation of 8-hydroxy-5-nitroquinoline based on the nitrosation of 8-hydroxyquinoline and subsequent oxidation of the nitroso derivative using nitric acid. The conditions for the nitrosation and oxidation of the 8-hydroxyquinoline (concentration of nitric acid, temperature, and reaction time) were optimized. A method for purifying the target compound is presented.
- Isaev,Lomovskii,Korolev,Karimov
-
p. 1027 - 1030
(2007/10/03)
-
- Quinone imines with a fused azine ring: I. Synthesis and hydrochlorination of 5-(p-tolylsulfonylimino)quinolin-8-one
-
5-(p-Tolylsulfonylimino)quinolin-8-one was synthesized, and its reaction with hydrogen chloride was studied. The reaction leads to formation of 7-chloro-8-hydroxy-5-(p-tolylsulfonylamino)quinoline hydrochloride.
- Belov,Nichvoloda
-
-
- Nitration of nitrogen heterocycles using microwaves
-
A comparative study of reaction time and yields for nitration of nitrogeneous heterocyclic compounds using Cu(NO3)2, KNO3 and NaNO3 under microwave irradiation as well as by conventional heating is reported.
- Kidwai, Mazaahir,Kohli, Seema
-
p. 1071 - 1073
(2007/10/03)
-
- Micellar catalysis of organic reactions. Part 37. A comparison of the catalysis of ester and amide hydrolysis by copper-containing micelles
-
The hydrolysis of a number of nitroactivated esters and amides has been studied in the presence of copper-containing metallomicelles at neutral pH. The relative rates of hydrolysis in the pure metallomicelle and in co-micelles with either cetyltrimethylammonium bromide (ctab) or Triton X-100 depends on the hydrophobicity of the substrate and whether it is completely solubilized by the copper micelle. Thus it depends on the concentration of the copper micelle. At low concentrations of copper micelle (0.2 mM) where the substrate is incompletely solubilized, the reaction is faster when 2 mM crab is added. At higher concentrations (>0.6 mM) where the substrate may be almost completely solubilized by the copper micelle, the reaction is slower when 2 mM crab is added. For ester hydrolysis the presence of either a carboxylic acid group or a heterocyclic nitrogen atom close to the reaction centre resulted in much larger catalysis by the metallomicelle than for model compounds without these additional groups. It is postulated that these groups coordinate with the metal ion and thus present the reaction centre close to a metal-bound hydroxyl resulting in a significant increase in the rate of bond formation, which is the rate-determining step for ester hydrolysis. For amide hydrolysis the presence of a carboxyl group ortho to the reaction centre did not lead to larger catalysis by the copper micelle than for the compound without this group. This difference is attributed to the different rate-determining steps for amide and for ester hydrolysis.
- Broxton,Nasser
-
p. 202 - 206
(2007/10/03)
-
- Catalytic hydrolysis of phosphate esters by metallocomplexes of 1,10-phenanthroline derivatives in micellar solution
-
Divalent metal-ion complexes of 2,9-bis-1,10-phenanthroline (C12Phen-MII) in neutral Brij 35 micelles catalyse the hydrolysis of various phosphate triesters, diesters and monoesters.The catalytic activity of C12Phen-MII has been compared with that of the metal-ion complexes of its water-soluble counterpart 2,9-bis-1,10-phenanthroline (C1Phen-MII).Saturation kinetics provide evidence for preliminary formation of ligand-MII-phosphate ester complexes, which decay to products.The hydroysis of diphenyl 4-nitrophenyl phosphate (1b) coordinated to C12Phen-ZnII proceeds 8700 times faster than the hydrolysis of 1b in the absence of metallocatalyst.Kinetic studies indicate that phosphate triesters containing a metal-ion-binding site in close proximity to the phosphoryl bond, i.e., diphenyl 5-nitro-2-pyridyl phosphate (2b) and diphenyl 5-nitro-8-quinolyl phosphate (3), are hydrolysed by the same mechanism as 1b.
- Weijnen, John G. J.,Engbersen, Johan F. J.
-
p. 351 - 357
(2007/10/02)
-
