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

Research output: Contribution to journalJournal articleResearchpeer-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 languageEnglish
JournalMedChemComm
Volume3
Issue number6
Pages (from-to)659-662
ISSN2040-2503
DOIs
Publication statusPublished - 2012
Externally publishedYes

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

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