4008-48-4Relevant articles and documents
Synthesis, characterization, computational and biological study of novel azabenzo[a]phenothiazine and azabenzo[b]phenoxazine heterocycles as potential antibiotic agent
Ibeanu, Fidelia N.,Onoabedje, Efeturi A.,Ibezim, Akachukwu,Okoro, Uchechukwu C.
, p. 1093 - 1102 (2018)
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.
Design, synthesis, and evaluation of multitarget-directed selenium-containing clioquinol derivatives for the treatment of Alzheimer's disease
Wang, Zhiren,Wang, Yali,Li, Wenrui,Mao, Fei,Sun, Yang,Huang, Ling,Li, Xingshu
, p. 952 - 962 (2014)
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).
Synthesis and anti-phytopathogenic activity of 8-hydroxyquinoline derivatives
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)
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.
Palladium catalyzed transformation and antimicrobial screening of novel angular azaphenothiazines
Godwin-Nwakwasi,Okoro,Ijeomah,Agbo,Ezeokonkwo
, p. 742 - 748 (2017/02/10)
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.
