scholarly journals Antitumor Agents 286. Design, Synthesis, and Structure−Activity Relationships of 3′R,4′R-Disubstituted-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DSP) Analogues as Potent Chemosensitizers to Overcome Multidrug Resistance

2010 ◽  
Vol 53 (24) ◽  
pp. 8700-8708 ◽  
Author(s):  
Ting Zhou ◽  
Qian Shi ◽  
Kenneth F. Bastow ◽  
Kuo-Hsiung Lee
Keyword(s):  
Multidrug Resistance ◽  
Antitumor Agents ◽  
Design Synthesis ◽  
Structure Activity Relationships ◽  
Structure Activity

Design, Synthesis and Structure−Activity Relationships of Novel Taxane-Based Multidrug Resistance Reversal Agents

2005 ◽  
Vol 48 (6) ◽  
pp. 2218-2228 ◽  
Author(s):  
Iwao Ojima ◽  
Christopher P. Borella ◽  
Xinyuan Wu ◽  
Pierre-Yves Bounaud ◽  
Cecilia Fumero Oderda ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Design Synthesis ◽  
Reversal Agents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Resistance Reversal

scholarly journals Structure activity relationships and the binding mode of quinolinone-pyrimidine hybrids as reversal agents of multidrug resistance mediated by P-gp

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerónimo Laiolo ◽  
Priscila Ailin Lanza ◽  
Oscar Parravicini ◽  
Cecilia Barbieri ◽  
Daniel Insuasty ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Molecular Complexes ◽  
Binding Mode ◽  
Reversal Agents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Doxorubicin Toxicity ◽  
Key Residues ◽  
Nanomolar Range ◽  
Experimental Structure

AbstractP-gp-associated multidrug resistance is a major impediment to the success of chemotherapy. With the aim of finding non-toxic and effective P-gp inhibitors, we investigated a panel of quinolin-2-one-pyrimidine hybrids. Among the active compounds, two of them significantly increased intracellular doxorubicin and rhodamine 123 accumulation by inhibiting the efflux mediated by P-gp and restored doxorubicin toxicity at nanomolar range. Structure–activity relationships showed that the number of methoxy groups, an optimal length of the molecule in its extended conformation, and at least one flexible methylene group bridging the quinolinone to the moiety bearing the pyrimidine favored the inhibitory potency of P-gp. The best compounds showed a similar binding pattern and interactions to those of doxorubicin and tariquidar, as revealed by MD and hybrid QM/MM simulations performed with the recent experimental structure of P-gp co-crystallized with paclitaxel. Analysis of the molecular interactions stabilizing the different molecular complexes determined by MD and QTAIM showed that binding to key residues from TMH 4–7 and 12 is required for inhibition.

scholarly journals Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 3041
Author(s):  
Xiaohan Hu ◽  
Sheng Tang ◽  
Feiyi Yang ◽  
Pengwu Zheng ◽  
Shan Xu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Design Synthesis ◽  
Structure Activity ◽  
Excellent Activity ◽  
Ic50 Values ◽  
Mcf 7

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure–activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

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