1-4-dihydroquinoline has been researched along with Neoplasms* in 3 studies
3 other study(ies) available for 1-4-dihydroquinoline and Neoplasms
| Article | Year |
|---|---|
A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy.
Intrinsic and acquired drug resistance and induction of secondary malignancies limit successful chemotherapy. Because mutagenic translesion synthesis (TLS) contributes to chemoresistance as well as treatment-induced mutations, targeting TLS is an attractive avenue for improving chemotherapeutics. However, development of small molecules with high specificity and in vivo efficacy for mutagenic TLS has been challenging. Here, we report the discovery of a small-molecule inhibitor, JH-RE-06, that disrupts mutagenic TLS by preventing recruitment of mutagenic POL ζ. Remarkably, JH-RE-06 targets a nearly featureless surface of REV1 that interacts with the REV7 subunit of POL ζ. Binding of JH-RE-06 induces REV1 dimerization, which blocks the REV1-REV7 interaction and POL ζ recruitment. JH-RE-06 inhibits mutagenic TLS and enhances cisplatin-induced toxicity in cultured human and mouse cell lines. Co-administration of JH-RE-06 with cisplatin suppresses the growth of xenograft human melanomas in mice, establishing a framework for developing TLS inhibitors as a novel class of chemotherapy adjuvants. Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Cisplatin; DNA Damage; DNA-Directed DNA Polymerase; Female; Gene Knockdown Techniques; Humans; Mad2 Proteins; Mice; Mice, Nude; Mice, Transgenic; Mutagenesis; Neoplasms; Nucleotidyltransferases; Quinolines; Transfection; Tumor Burden; Xenograft Model Antitumor Assays | 2019 |
Design of new hybrid template by linking quinoline, triazole and dihydroquinoline pharmacophoric groups: A greener approach to novel polyazaheterocycles as cytotoxic agents.
A new hybrid template designed by linking three pharmacophoric groups, for example, quinoline, triazole and dihydroquinoline moieties have been used for the generation of a library of molecules as potential cytotoxic agents. Synthesis of these polyazaheterocycles were carried out by using a strategy that involved one-pot sequential azidation and CuAAC in water under mild conditions. A number of 1,4-disubstituted 1,2,3-triazoles possessing quinolinylmethylene at N-1 and 1,2-dihydroquinolinyl methylene at C-4 as different substituents were synthesized and evaluated for their cytotoxic effects against various cancer cells. Some of them showed encouraging activities against lung cancer cells and one of them showed inhibition of PDE4 indicating the potential medicinal value of these novel polyazaheterocycles. Topics: Antineoplastic Agents; Aza Compounds; Azides; Cell Line, Tumor; Drug Design; Green Chemistry Technology; Humans; Molecular Docking Simulation; Neoplasms; Phosphodiesterase 4 Inhibitors; Quinolines; Triazoles | 2015 |
Discovery of substituted 1,4-dihydroquinolines as novel promising class of P-glycoprotein inhibitors: First structure-activity relationships and bioanalytical studies.
Multidrug resistance (mdr) is the most important problem in the therapeutical treatment of cancer. One central problem in the resistance proceeding is the expression of transmembrane efflux pumps which transport drugs out of the cells. We developed novel substituted 1,4-dihydroquinolines as inhibitors of the transmembrane efflux pump P-glycoprotein. Structure-activity relationships are discussed for this first series. Promising active inhibitors have been identified and first bioanalytical studies have been carried out to address questions of cellular toxicity, P-gp substrate as well as mdr reversal properties. Topics: Animals; ATP Binding Cassette Transporter, Subfamily B; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Mice; Neoplasms; Quinolines; Structure-Activity Relationship | 2015 |