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 | |
| Publication status | Published - 2012 |
| Externally published | Yes |
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
