206874-57-9Relevant academic research and scientific papers
Reversal of P-gp and BCRP-mediated MDR by tariquidar derivatives
Li, Xu-Qin,Wang, Lin,Lei, Yan,Hu, Tao,Zhang, Fei-Long,Cho, Chi-Hin,To, Kenneth K.W.
, p. 560 - 572 (2015)
Abstract With an aim to generate non-toxic, specific and highly potent multidrug resistance (MDR) modulators, a novel series of anthranilic acid amide-substituted tariquidar derivatives were synthesized. The new compounds were evaluated for their cytotoxicity toward normal human colon fibroblasts (CCD18-Co), human gastric epithelial cell line (HFE) and primary rat liver cells, and for their ability to inhibit P-gp/BCRP-mediated drug efflux and reversal of P-gp and BCRP-mediated MDR in parental and drug-resistant cancer cell lines (LCC6 MDR1, MCF-7 FLV1000, R-HepG2, SW620-Ad300). While tariquidar is highly toxic to normal cells, the new derivatives exhibited much lower or negligible cytotoxicity. Some of the new tariquidar derivatives inhibited both P-gp and BCRP-mediated drug efflux whereas a few of them bearing a sulfonamide functional group (1, 5, and 16) are specific to P-gp. The new compounds were also found to potentiate the anticancer activity of the transporter substrate anticancer drugs in the corresponding transporter-overexpressing cell lines. The extent of resistance reversal was found to be consistent with the transporter inhibitory effect of the new derivatives. To further understand the mechanism of P-gp and BCRP inhibition, the tariquidar derivatives were found to interact with the transporters using an antibody-based UIC2 or 5D3 shift assay. Moreover, the transporters-inhibiting derivatives were found to modulate the ATPase activities of the two MDR transporters. Our data thus advocate further development of the new compounds for the circumvention of MDR.
Anthranilic acid derivatives, their preparation and their use in medicine
-
, (2018/05/24)
The invention relates to an anthranilic acid derivative, a preparation method and application thereof in medicine. Specifically, the invention relates the nthranilic acid derivative shown as general formula (I), a preparation method and a pharmaceutical c
Synthesis and biological evaluation of a small molecule library of 3rd generation multidrug resistance modulators
Klinkhammer, Werner,Mueller, Henrik,Globisch, Christoph,Pajeva, Ilza K.,Wiese, Michael
experimental part, p. 2524 - 2535 (2009/09/05)
The development of new modulators possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcoming P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in tumour cells. In this study 39 compounds are presented which hav
