Identification of Novel Piperazinylquinoxaline Derivatives as Potent Phosphoinositide 3-Kinase (PI3K) Inhibitors

Wu, Peng; Su, Yi; Guan, Xianghong; Liu, Xiaowen; Zhang, Jiankang; Dong, Xiaowu; Huang, Wenhai; Hu, Yongzhou

doi:10.1371/journal.pone.0043171

Cited by 4 publications

(3 citation statements)

References 24 publications

(25 reference statements)

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“…Wu et al [ 83 ] identified novel piperidinylquinoxalines (242) and piperazinylquinoxalines (243-246) as PI3Kα inhibitors, with previously identified morpholinoquinoxaline derivative 240 (PI3Kα IC 50 =0.44 µM) and piperidinylquinoxaline derivative 241 (PI3Kα IC 50 = 0.025 µM) as the lead. Modification at the 2-position of the quinoxaline scaffold and 4-substituent of phenylsulfonyl moiety led to novel PI3Kα inhibitors with good to potent inhibitory activity (up to 24 nM).…”

Section: Pyridines Quinolines Indoles and Indazolesmentioning

confidence: 99%

Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents

Liu

Wan

et al. 2016

Oncotarget

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Section: Pyridines Quinolines Indoles and Indazolesmentioning

confidence: 99%

Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents

Liu

Wan

et al. 2016

Oncotarget

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“…Similarly, NVP-BEZ235, a dual PI3K/mTOR inhibitor, has antitumor activity in human GBM [41]. Several other PI3K inhibitors are being developed and evaluated [42,43].…”

Section: Pi3k/akt Signalingmentioning

confidence: 99%

Targeting Glioma Stem Cells for Therapy: Perspectives and Challenges

Saito¹

2015

J Cell Sci Ther

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Glioblastoma multiforme (GBM, WHO grade IV) is the most aggressive and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. Recent studies indicate that some neoplastic cells within human high-grade glioma have the capacity for self-renewal and multi-lineage differentiation, properties associated with normal neural stem cells. These stem-like tumor cells known as GBM stem cells (GSCs) are responsible for tumor progression and recurrence. Therefore, GSCs are attractive targets for novel glioma therapies. Mounting studied have evidenced that some molecular signaling pathways (including EGFR, PI3K, PDGFR, TGF and Notch.), which are critically important for GSCs self-renew and proliferation, are activated by genetically mutation or amplification in GSCs. Targeting these molecules might be promising novel treatment strategies to eliminate GSCs, however, crosstalk and compensation between different signaling pathways as well as intratumoral heterogeneity make it more complicate and a big challenge.

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“…Quinoxaline nucleus forms an important part of active pharmacophore in synthesis of wide range of biological active compounds used as antibacterial, 27,28 antiviral, 29,30 anti-HIV, 31 antimalarial, 32,33 anticancer, [34][35][36] antitubercular, 37 antileishmanial, 38 and various neurological disorders. 39,40 Based on our interest in sustainable green chemistry, herein, we have developed a methodology where complex ketones which have pharmacologically important moiety can be reduced using a cheap and easy process with D carota as the catalyst.…”

Section: Introductionmentioning

confidence: 99%

Green synthesis of enantiopure quinoxaline alcohols using Daucus carota

et al. 2019

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Green chemistry comprises a new approach in the synthesis of biologically active compounds using biocatalysts, thus diminishing the hazards for human health and environmental pollution. Asymmetric bioreduction is one of the most widely employed strategies in chemoenzymatic synthesis to produce enantiomerically pure chiral alcohols. The present study highlights the use biocatalyst Daucus carota for selective bioreduction of quinoxaline ketones 1a-6a to their corresponding optically pure alcohols 1b-6b in high yields (up to 84%) and good enantioselectivity (up to 98%). The absolute configuration of the chiral product (R)-1-(3-methyl 7-nitroquinoxalin-2-yl) ethan-1-ol 2b was confirmed by X-ray crystallography studies. The chiral R-configuration of the products obtained was confirmed by absolute configuration studies and was assigned following anti-Prelogs rule. Quinoxaline pharmacophores form a part of well-known potent drug molecules; hence, the chiral products were studied for determination of their molecular properties using SwissADME property analyser. All the chiral products show no Lipinski rule violations and are expected to have good oral bioavailability. As per the molecular properties prediction studies, the compound 6b (R)-1- (6,7-dichloro-3-methylquinoxalin-2-yl) ethanol is observed to show the best physicochemical properties to be a good lead molecule. Thus, the sustainable methodology was developed, and it confirms the synthesis of novel quinoxaline chiral alcohols in a simple, inexpensive, and eco-friendly condition using D carota.

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Identification of Novel Piperazinylquinoxaline Derivatives as Potent Phosphoinositide 3-Kinase (PI3K) Inhibitors

Cited by 4 publications

References 24 publications

Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents

Recent development of ATP-competitive small molecule phosphatidylinostitol-3-kinase inhibitors as anticancer agents

Targeting Glioma Stem Cells for Therapy: Perspectives and Challenges

Green synthesis of enantiopure quinoxaline alcohols using Daucus carota

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