کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1393880 | 1501108 | 2016 | 11 صفحه PDF | دانلود رایگان |
• A series of novel 7- or 8-substituted 4-morpholine-quinazoline derivatives were synthesized.
• 17f exhibited excellent inhibitory activities against PI3K and mTOR.
• Docking studies were performed to gain insight about protein–ligand interactions.
• The work has excellent scope to probe further structure activity relationships.
In this study, a series of novel 7 or 8-substituted 4-morpholine-quinazoline derivatives was designed and synthesized. Their PI3Kα inhibitory activities, antiproliferative activities against seven cancer cell lines, namely, PC-3, DU145, MCF-7, BT474, SK-BR-3, U937 and A431, were evaluated in vitro. Compound 17f proved to be a potential drug candidate with high PI3Kα inhibition activity (IC50 = 4.2 nM) and good antiproliferative activity. Compound 17f was also tested for its inhibitory activities against other kinases, such as PI3Kβ, PI3Kγ, PI3Kδ and mTOR, its effects on p-Akt (S473) and cell cycle. These results suggested that compound 17f could significantly inhibit the PI3K/Akt/mTOR pathway as a potent PI3K inhibitor and anticancer agent.
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Journal: European Journal of Medicinal Chemistry - Volume 108, 27 January 2016, Pages 644–654