Abstract
In present study, a series of N-(2-methoxy-5-(3-substituted quinazolin-4(3H)-one-6-yl)-pyridin-3-yl)phenylsulfonamide were synthesized. Their antiproliferative activities in vitro were evaluated via MTT assay against HCT116 and MCF-7 cancer cell lines. The SAR of title compounds was discussed. The compounds (S)-C5 and (S)-C8 displayed potent inhibitory activity against PI3Ks and mTOR, especially against PI3Kα. In addition, compound (S)-C5 can efficaciously inhibit tumor growth in a mice S-180 model. These findings suggest that our designed compounds can serve as potent PI3K inhibitors and effective anticancer agents.
Keywords:
Antitumor activity; PI3K inhibitor; Quinazolin-4(3H)-ones; Synthesis.
Copyright © 2015. Published by Elsevier Ltd.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / therapeutic use*
-
Cell Line, Tumor
-
Class I Phosphatidylinositol 3-Kinases
-
Humans
-
Mice
-
Models, Molecular
-
Neoplasms / drug therapy*
-
Neoplasms / metabolism
-
Phosphatidylinositol 3-Kinases / metabolism
-
Phosphoinositide-3 Kinase Inhibitors*
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / therapeutic use
-
Quinazolinones / chemical synthesis
-
Quinazolinones / chemistry*
-
Quinazolinones / therapeutic use*
-
TOR Serine-Threonine Kinases / antagonists & inhibitors
-
TOR Serine-Threonine Kinases / metabolism
Substances
-
Antineoplastic Agents
-
Phosphoinositide-3 Kinase Inhibitors
-
Protein Kinase Inhibitors
-
Quinazolinones
-
4-hydroxyquinazoline
-
Class I Phosphatidylinositol 3-Kinases
-
PIK3CA protein, human
-
TOR Serine-Threonine Kinases