Discovery of 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides as novel PI3K inhibitors and anticancer agents by bioisostere

Shao, Teng; Wang, Juan; Chen, Jiangang; Li, Huan; Li, Yiping; Li, Yan; Yang, Guangde; Mei, Qibing; Zhang, San‐Qi

doi:10.1016/j.ejmech.2014.01.053

Cited by 36 publications

(12 citation statements)

References 23 publications

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“…The values listed in Table 6 display the comparison of the solubility of S 1 , S 2 , and S 3 in each solvent. The results revealed that in different solvents except acetone and ethyl acetate, the solubility of S 2 was the highest and that of S 3 was the lowest; however, S 1 had the medium solubility, which was consistent with the antiproliferative activity demonstrated in our previous study [3]. The solubility of S 2 was the highest and that of S 1 was the lowest in acetone.…”

Section: Resultssupporting

confidence: 92%

“…Compounds S 1 (melting point: 168.5-170.5°C), S 2 (melting point: 146-147°C), and S 3 (melting point: 141-142°C) were synthesized in the laboratory during our previous study and the structures were confirmed by nuclear magnetic resonance spectroscopy and high resolution mass spectroscopy [3]. The methods for the synthesis of three compounds and the characterization of their structures have been described in detail in our published study.…”

Section: Methodsmentioning

confidence: 99%

“…3-(4-fluorophenylsulfonamido)-2-methoxy-5-(4-morpholinoquinazolin-6-yl)benzamide (S 1 ), 2-methoxy-3-(4-methylphenylsulfonamido)-5-(4-morpholinoquinazolin-6-yl)benzamide (S 2 ), and 3-(4-fluorophenylsulfonamido)-2-methoxy-5-(4-morpholinoquinolin-6-yl)benzamide (S 3 ) were found to be three novel PI3K inhibitors and anticancer agents against A549, HCT116, U87MG, and KB cell lines in our previous study [3]. Fig.…”

Section: Introductionmentioning

confidence: 98%

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Solubility of three types of benzamide derivatives in toluene, ethyl acetate, acetone, chloroform, methanol, and water at temperatures ranging from 288.15 to 328.15K at atmospheric pressure

Chen

Nan

Yang

et al. 2015

Journal of Molecular Liquids

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Section: Resultssupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Solubility of three types of benzamide derivatives in toluene, ethyl acetate, acetone, chloroform, methanol, and water at temperatures ranging from 288.15 to 328.15K at atmospheric pressure

Chen

Nan

Yang

et al. 2015

Journal of Molecular Liquids

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“…Using our established system, we screened several series of compounds, including compounds labelled W (N-(prop-2-ynyl)-4-(substituted phenylcarbonylamino) benzamides) [21], compounds labelled K (2-arylisoquinoline-1, 3(2H, 4H)-diones [22], compounds labelled Z (N-aryl salicylamides) [23], compounds labelled X (diaryl urea) [24], and compounds labelled S (5-(2-aminobenzo[d] hiazole-6-yl)-2-methoxy-3-(phenylsulfonylamino) benzamides) [25]. …”

Section: Methodsmentioning

confidence: 99%

Identification and application of anti-inflammatory compounds screening system based on RAW264.7 cells stably expressing NF-κB-dependent SEAP reporter gene

Ren

Lan

et al. 2017

BMC Pharmacol Toxicol

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BackgroundNF-κB is one of the key transcription factors in the inflammatory response, transactivates a series of pro-inflammatory genes and is therefore regarded as an important target for anti-inflammatory drug screening.MethodWe recombined the reporter gene vector with inserting the “neo” transcript into the vector pNF-κB-SEAP, made the reporter gene vector stable in a eukaryotic cell line. The recombinant reporter gene vector we named pNF-κB-SEAP-Neo was transfected into RAW264.7. We selected the transfected RAW264.7 cell line with G418 for 15 days and then get RAW264.7 cells stably expressing NF-κB-dependent SEAP named as RAW264.7-pNF-κB-SEAP cells. We treated the RAW264.7-pNF-κB-SEAP cells with NF-κB agonists as LPS, PolyI:C and TNF-α, NF-κB inhibitor as PDTC and BAY117085, in different concentrations and time points and tested the expression of the SEAP, constructed the drug screening system on the base of the RAW264.7-pNF-κB-SEAP cell line. 130 chemicals were screened with the drug screening system we constructed and one of these chemicals numbered w10 was found could inhibit the NF-κB significantly. At last, we verified the inhibition of w10 to expression of genes promoted with NF-κB in HepG2 and Hela, and to migration of Hela.ResultIn this study, we established a drug screening system based on RAW264.7 cells that stably expressed the NF-κB-dependent, SEAP reporter gene. To develop a standard method for drug screening using this reporter-gene cell line, the test approach of SEAP was optimized and basic conditions for drug screening were chosen. This included the initial cell number inoculated in a 96-well plate, the optimum agonist, inhibitor of NF-κB pathway and their concentrations during screening. Subsequently, 130 newly synthesized compounds were screened using the stable reporter-gene cell line. The anti-inflammatory effects of the candidate compounds obtained were further verified in 2 cancer cell lines. The results indicated that compound W10 (methyl 4-(4-(prop-2-yn-1-ylcarbamoyl) phenylcarbamoyl) benzoate) significantly inhibited SEAP production under the screening conditions. Further results confirmed that the precursor compound significantly inhibited the transcription of NF-κB target genes.ConclusionIn conclusion, RAW264.7 cells, stably expressing the NF-κB-dependent SEAP-reporter gene, may provide a new, feasible, and efficient cellular drug-screening system.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-016-0113-6) contains supplementary material, which is available to authorized users.

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“…However, a definite demonstration that these enzymes are relevant in vivo is lacking as most published studies have only studied the effects of pan PI3K inhibitors, especially wortmannin and LY294002, in preclinical models of inflammation resolution. There are now many new selective PI3K inhibitors in development [60]. Whether such drugs with greater selectivity and safety profile will resolve inflammation in vivo needs to be studied.…”

Section: Signaling Molecules As Crucial Regulators Of the Resolutimentioning

confidence: 99%

Switching Off Key Signaling Survival Molecules to Switch On the Resolution of Inflammation

Perez

Vago

Athayde

et al. 2014

Mediators of Inflammation

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Inflammation is a physiological response of the immune system to injury or infection but may become chronic. In general, inflammation is self-limiting and resolves by activating a termination program named resolution of inflammation. It has been argued that unresolved inflammation may be the basis of a variety of chronic inflammatory diseases. Resolution of inflammation is an active process that is fine-tuned by the production of proresolving mediators and the shutdown of intracellular signaling molecules associated with cytokine production and leukocyte survival. Apoptosis of leukocytes (especially granulocytes) is a key element in the resolution of inflammation and several signaling molecules are thought to be involved in this process. Here, we explore key signaling molecules and some mediators that are crucial regulators of leukocyte survival in vivo and that may be targeted for therapeutic purposes in the context of chronic inflammatory diseases.

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Discovery of 2-methoxy-3-phenylsulfonamino-5-(quinazolin-6-yl or quinolin-6-yl)benzamides as novel PI3K inhibitors and anticancer agents by bioisostere

Cited by 36 publications

References 23 publications

Solubility of three types of benzamide derivatives in toluene, ethyl acetate, acetone, chloroform, methanol, and water at temperatures ranging from 288.15 to 328.15K at atmospheric pressure

Solubility of three types of benzamide derivatives in toluene, ethyl acetate, acetone, chloroform, methanol, and water at temperatures ranging from 288.15 to 328.15K at atmospheric pressure

Identification and application of anti-inflammatory compounds screening system based on RAW264.7 cells stably expressing NF-κB-dependent SEAP reporter gene

Switching Off Key Signaling Survival Molecules to Switch On the Resolution of Inflammation

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