Discovery of novel morpholino-quinoxalines as PI3K alpha inhibitors by pharmacophore-based screening

Peng Wu; Yi Su; Xiaowen Liu; Jingying Yan; Yong Ye; Lei Zhang; Jianchao Xu; Shaoyu Weng; Yani Li; Tao Liu; Xiaowu Dong

doi:10.1039/c2md00255h

Discovery of novel morpholino-quinoxalines as PI3K alpha inhibitors by pharmacophore-based screening

Peng Wu
, Yi Su
, Xiaowen Liu
, Jingying Yan
, Yong Ye
, Lei Zhang
, Jianchao Xu
, Shaoyu Weng
, Yani Li
, Tao Liu
, Xiaowu Dong

Zhejiang University

Research output: Contribution to journal › Journal article › Research › peer-review

Abstract

A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.

Original language	English
Journal	MedChemComm
Volume	3
Issue number	6
Pages (from-to)	659-662
ISSN	2040-2503
DOIs	https://doi.org/10.1039/c2md00255h
Publication status	Published - 2012
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

drug discovery
Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] HCT 116 cell line cell_line human colon cancer cells PC3 cell line cell_line human prostate cancer cells HL60 cell line cell_line human promyelocytic leukemia cells A549 cell line cell_line lung adenocarcinoma epithelial cells
morpholino
morpholino-quinoxalines enzyme inhibitor-drug
phosphoinositol 3-kinase-alpha
sulfonyl group
02508, Cytology - Human
12512, Pathology - Therapy
22002, Pharmacology - General
22005, Pharmacology - Clinical pharmacology
DiscoveryStudio 2.0 package computer software
molecular docking mathematical and computer techniques
pharmacophore mapping analysis laboratory techniques
pharmacophore-based screening laboratory techniques
Pharmacology

Access to Document

10.1039/c2md00255h

OpenUrl availability

Check availability in DTU Findit

Cite this

@article{7beed20cd8184e01b0843d1a1f664968,

title = "Discovery of novel morpholino-quinoxalines as PI3K alpha inhibitors by pharmacophore-based screening",

abstract = "A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.",

keywords = "drug discovery, Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] HCT 116 cell line cell\_line human colon cancer cells PC3 cell line cell\_line human prostate cancer cells HL60 cell line cell\_line human promyelocytic leukemia cells A549 cell line cell\_line lung adenocarcinoma epithelial cells, morpholino, morpholino-quinoxalines enzyme inhibitor-drug, phosphoinositol 3-kinase-alpha, sulfonyl group, 02508, Cytology - Human, 12512, Pathology - Therapy, 22002, Pharmacology - General, 22005, Pharmacology - Clinical pharmacology, DiscoveryStudio 2.0 package computer software, molecular docking mathematical and computer techniques, pharmacophore mapping analysis laboratory techniques, pharmacophore-based screening laboratory techniques, Pharmacology",

author = "Peng Wu and Yi Su and Xiaowen Liu and Jingying Yan and Yong Ye and Lei Zhang and Jianchao Xu and Shaoyu Weng and Yani Li and Tao Liu and Xiaowu Dong",

year = "2012",

doi = "10.1039/c2md00255h",

language = "English",

volume = "3",

pages = "659--662",

journal = "MedChemComm",

issn = "2040-2503",

publisher = "Royal Society of Chemistry",

number = "6",

}

TY - JOUR

T1 - Discovery of novel morpholino-quinoxalines as PI3K alpha inhibitors by pharmacophore-based screening

AU - Wu, Peng

AU - Su, Yi

AU - Liu, Xiaowen

AU - Yan, Jingying

AU - Ye, Yong

AU - Zhang, Lei

AU - Xu, Jianchao

AU - Weng, Shaoyu

AU - Li, Yani

AU - Liu, Tao

AU - Dong, Xiaowu

PY - 2012

Y1 - 2012

N2 - A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.

AB - A pharmacophore model of PI3K alpha inhibitors was built using the DiscoveryStudio 2.0 package. Pharmacophore-based screening (PBS) retrieved a series of novel morpholino-quinoxalines as PI3K alpha inhibitors, as exemplified by 1a (PI3K alpha IC50: 0.44 mu M). All target compounds showed good in vitro cytotoxicity against tested human cell lines. A pharmacophore mapping analysis and docking study indicated that both the morpholino group and the sulfonyl group contributed significantly to the potent PI3K alpha inhibitory activity and cytotoxicity of the compounds.

KW - drug discovery

KW - Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] HCT 116 cell line cell_line human colon cancer cells PC3 cell line cell_line human prostate cancer cells HL60 cell line cell_li

KW - morpholino

KW - morpholino-quinoxalines enzyme inhibitor-drug

KW - phosphoinositol 3-kinase-alpha

KW - sulfonyl group

KW - 02508, Cytology - Human

KW - 12512, Pathology - Therapy

KW - 22002, Pharmacology - General

KW - 22005, Pharmacology - Clinical pharmacology

KW - DiscoveryStudio 2.0 package computer software

KW - molecular docking mathematical and computer techniques

KW - pharmacophore mapping analysis laboratory techniques

KW - pharmacophore-based screening laboratory techniques

KW - Pharmacology

U2 - 10.1039/c2md00255h

DO - 10.1039/c2md00255h

M3 - Journal article

SN - 2040-2503

VL - 3

SP - 659

EP - 662

JO - MedChemComm

JF - MedChemComm

IS - 6

ER -

Discovery of novel morpholino-quinoxalines as PI3K alpha inhibitors by pharmacophore-based screening

Abstract

UN SDGs

Keywords

Access to Document

OpenUrl availability

Fingerprint

Cite this