Abstract
A series of 1,2-dihydroquinoline derivatives were synthesized and evaluated for cytotoxicity in HeLa, Hep G2 and 6HEK-293T cell lines. EEDQ2 was identified as a promising anti-cancer agent with low IC50 in HeLa (18.55μg/ml) and Hep G2 (14.53μg/ml) cells. For improving the antitumor activity and tumor selectivity of EEDQ2, we prepared transferrin (Tf)-modified liposomes (LPs) to deliver EEDQ2. When HeLa and Hep G2 cells were treated with LP-delivered EEDQ2, the ROS level was significantly enhanced, and mitochondrial membrane potential was reversed. Tf-LPs improved cell uptake of EEDQ2 by about 3.7 times compared with non-targeted LPs. These data suggest that Tf-LPs delivering EEDQ2 is a promising strategy to treat cancer.
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Cell Survival / drug effects
-
Drug Carriers / chemistry
-
Drug Liberation
-
HEK293 Cells
-
HeLa Cells
-
Hep G2 Cells
-
Humans
-
Inhibitory Concentration 50
-
Liposomes / chemistry*
-
Liposomes / ultrastructure
-
Membrane Potential, Mitochondrial / drug effects
-
Microscopy, Confocal
-
Microscopy, Electron, Scanning
-
Molecular Structure
-
Quinolines / chemistry*
-
Reactive Oxygen Species / metabolism
-
Transferrin / chemistry*
Substances
-
Antineoplastic Agents
-
Drug Carriers
-
Liposomes
-
Quinolines
-
Reactive Oxygen Species
-
Transferrin
-
EEDQ
Grants and funding
This research was supported by the National Natural Science Foundation of China (grant no. 81502999) and Jilin Province Science and Technology Development Program (grant no. 20170414039GH).