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.
Benzo[c, d]indolyl-2(H)-one-polyamine conjugate and preparation method and application thereof
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, (2017/10/10)
The invention relates to a benzo[c, d]indolyl-2(H)-one-polyamine conjugate or pharmaceutical salt thereof. The benzo[c, d]indolyl-2(H)-one-polyamine conjugate or the pharmaceutical salt thereof adopts the structure shown as a FORMULA I, wherein m is 1 or 2, n is 1, 2 or 3, R is FORMULA, and X is 1, 2 or 3. The invention provides a preparation method of the benzo[c, d]indolyl-2(H)-one-polyamine conjugate or the pharmaceutical salt thereof. In addition, tests find that the benzo[c, d]indolyl-2(H)-one-polyamine conjugate or the pharmaceutical salt thereof has high anti-tumor and tumor metastasis-inhibiting activity, and has a higher therapeutic index and has a prospect in preparing medicines for preventing and treating tumor metastasis when being compared with a positive control medicine amonafide,; and moreover, the benzo[c, d]indolyl-2(H)-one-polyamine conjugate or the pharmaceutical salt thereof can be located in cellular lysosome and can be used as a cellular lysosome-targeted fluorescent probe.