Synthesis and antiplasmodial activity of new 4-aryl-2-trichloromethylquinazolines

Verhaeghe, Pierre; Azas, Nadine; Gasquet, M.; Hutter, Sébastien; Ducros, Christophe; Laget, M.; Rault, Syl­vain; Rathelot, Pascal; Vanelle, Patrice

doi:10.1016/j.bmcl.2007.10.027

Cited by 143 publications

(64 citation statements)

References 22 publications

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“…anti-hypertension, 3 antimalaria, 4 antifungi 5 and other pharmacological effects. In recent years, as an active skeletal structure of pharmacodynamic activities, several quinazoline compounds have been successfully applied as anticancer drugs.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics analysis reveals aminoquinazolin derivative 9d-induced oxidative stress and cell cycle arrest in A549 cells

et al. 2017

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A novel aminoquinazolin derivative (named 9d), synthesized in our lab shows potential antitumor activity against A549 lung cancer cell lines. However, previous studies on the pharmacological mechanism of 9d mostly focused on cell and gene levels; the metabolic mechanism remains unknown. In this paper, an ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) based metabolomics approach was established to study the probable antitumor mechanism. Q-TOF MS and MS/MS were used to identify significantly different metabolites. 22 significantly different metabolites were observed between the 9d-treated A549 lung cells group and control group. They were involved in glycerophospholipid metabolism, glutathione metabolism, phenylalanine metabolism, cysteine and methionine metabolism, and aminoacyl-tRNA biosynthesis. The results showed that glutathione level and cell-membrane components phosphatidylcholines were decreased in 9d-treated cells, while their oxidative products, oxidized glutathione and lysophosphatidylcholines, were significantly increased. Further biological investigation showed an apparent accumulation of reactive oxygen species and a decrease in mitochondrial membrane potential.The results indicated that the aminoquinazolin derivative induced oxidative stress-mediated apoptosis.Moreover, phenylalanine metabolism suggested the up-regulation of L-phenylalanine might act as an endogenous drug carrier of 9d to improve cellular antiproliferation ability. The inhibition of aminoacyltransfer RNA and flow cytometry results indicated that cell cycle progression was blocked in the G1 phase, which was in accordance with the results obtained from some marketed aminoquinazolin derivatives. The above results proposed that 9d could induce oxidative stress and cell cycle arrest, which finally led to cell apoptosis in A549 cells. The study supplies a rapidly and highly active strategy to investigate the antitumor mechanism of drugs, which benefits its further improvement and development.

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Section: Introductionmentioning

confidence: 99%

Metabolomics analysis reveals aminoquinazolin derivative 9d-induced oxidative stress and cell cycle arrest in A549 cells

et al. 2017

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“…[20] In order to establish structure-activity relationships, pharmacomodulations were done, using palladium-catalyzed coupling reactions of a molecule bearing a bromine atom were investigated according to previously described studies. [26][27][28][29] Reaction parameters were assessed using 4-[5-(4-bromophenyl)-3-(4-fluorophenylsulfonyl)-5-methyl-4,5-dihydrofuran-2-yl]benzonitrile (22) as the substrate of p-tolylbenzeneboronic acid (Table 2), in order to optimize yields. Good yields were achieved with polar solvents only (DMF, toluene:ethanol); likewise, microwave irradiation leads to better yields and dramatically reduces reaction time.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…The reaction of cyano derivatives synthesized from both cyclization mediated by manganese(III) acetate and Suzuki-Miyaura cross-coupling reactions (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31), with hydroxylamine hydrochloride and potassium tert-butoxide in DMSO [30] led to conversion of the cyano group into amidoximes 32-51 in moderate to excellent yields (28-100%) as reported in Table 4. almost halves the reaction yield.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

New series of monoamidoxime derivatives displaying versatile antiparasitic activity

Tabelé

Cohen

Curti

et al. 2014

European Journal of Medicinal Chemistry

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Graphical abstractNew series of monoamidoxime derivatives displaying versatile antiparasitic activity. This suggests that the amidoxime scaffold has properties that could make it a promising new antiparasitic pharmacophore. M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT

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“…Especially, their importance as selective anticancer chemotherapy agents appears unparalleled and attracts the attention of many pharmaceutical research teams worldwide [10][11][12][13]. Focusing on quinazoline substrates, our group also quite recently described the preparation of new 2-substituted-quinazoline derivatives which exhibit original antiplasmodial properties [14][15][16].…”

Section: Open Accessmentioning

confidence: 99%

Regioselective Suzuki-Miyaura Reaction: Application to the Microwave-promoted Synthesis of 4,7-Diarylquinazolines

et al. 2010

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Synthesis and antiplasmodial activity of new 4-aryl-2-trichloromethylquinazolines

Cited by 143 publications

References 22 publications

Metabolomics analysis reveals aminoquinazolin derivative 9d-induced oxidative stress and cell cycle arrest in A549 cells

Metabolomics analysis reveals aminoquinazolin derivative 9d-induced oxidative stress and cell cycle arrest in A549 cells

New series of monoamidoxime derivatives displaying versatile antiparasitic activity

Regioselective Suzuki-Miyaura Reaction: Application to the Microwave-promoted Synthesis of 4,7-Diarylquinazolines

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