122248-82-2Relevant articles and documents
Potent P-glycoprotein inhibition of emodin derivative: Synthesis and biological evaluation
Wang, Jianhong,Gan, Ying,Li, Shaobin,Luo, Tianwei,Zhang, Yahong,Zhao, Jin
, p. 2106 - 2112 (2014)
A new series of emodin derivatives was prepared and evaluated for their in vitro antiproliferative activity. Preliminary results revealed that these derivatives exhibited weak or negligible cytotoxicity at 10 μM against various cancer cell lines (i.e., K562, HepG2, and HCT116 cell lines) as well as normal hepatic cells (QSG7701). Interestingly, the evaluation for P-glycoprotein (P-gp) modulation indicated that they possessed potent P-gp inhibitory activity. Among them, the effect of compound 6 on P-gp inhibition was even greater than that of Verapamil, the known P-gp modulator. Therefore, the natural emodin scaffold could be employed as safe and effective modulator of P-gp mediated drug resistance in cancer chemotherapy. Springer Science+Business Media 2013.
Thiazole orange – Spermine conjugate: A potent human telomerase inhibitor comparable to BRACO-19
Wang, Siwen,Yang, Dazhou,Singh, Mandeep,Joo, Hyun,Rangel, Vanessa M.,Tran, Aaron,Phan, Erich,Xue, Liang
, p. 20 - 33 (2019/05/06)
In this report, we synthesized a series of TO conjugates containing different amino side chains and investigated their binding to telomeric G-quadruplex DNA (G4) using several biophysical methods including fluorometric titration and thermal denaturation monitored by fluorescence and circular dichroism. The composition of side chains strongly affects the binding of these molecules to G-quadruplex DNA. Incorporation of amino side chains increases the binding affinity of TO toward G4 but has a minimal effect on its selectivity for G4 over duplex DNA. The plausible binding modes are a synergistic effect of end-stacking and groove interactions as indicated by docking studies. Inhibition of human telomerase activity by TO derivatives was determined in vitro by the TRAP assay. Several derivatives can selectively inhibit the activity of telomerase over DNA polymerase at low concentrations. More significantly, TO-spermine conjugate (16) exhibits a remarkable effect on telomerase inhibition in the submicromolar range, which is comparable to the inhibition effect of a well-known G4 ligand, BRACO-19. Our results here provide guidance of utilizing TO derivatives as a viable scaffold to design novel G4 ligands, G4 probes, and potent telomerase inhibitors.
Novel Polyamine-Naphthalene Diimide Conjugates Targeting Histone Deacetylases and DNA for Cancer Phenotype Reprogramming
Pasini, Alice,Marchetti, Chiara,Sissi, Claudia,Cortesi, Marilisa,Giordano, Emanuele,Minarini, Anna,Milelli, Andrea
supporting information, p. 1218 - 1223 (2017/12/26)
A series of hybrid compounds was designed to target histone deacetylases and ds-/G-quadruplex DNAs by merging structural features deriving from Scriptaid and compound 1. Compound 6 binds different DNA arrangements, inhibits HDACs both in vitro and in cells, and is able to induce a reduction of cell proliferation. Moreover, compound 6 displays cell phenotype-reprogramming properties since it prevents the epithelial to mesenchymal transition in cancer cells, inducing a less aggressive and migratory phenotype, which is one of the goals of present innovative strategies in cancer therapies.