Jatrophane Diterpenes as Modulators of Multidrug Resistance. Advances of Structure—Activity Relationships and Discovery of the Potent Lead Pepluanin A.

ChemInform ◽  
2004 ◽  
Vol 35 (28) ◽  
Author(s):  
Gabriella Corea ◽  
Ernesto Fattorusso ◽  
Virginia Lanzotti ◽  
Riccardo Motti ◽  
Pierre-Noel Simon ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Structure Activity Relationships ◽  
Structure Activity

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.

ChemInform Abstract: Flavonoid-Related Modulators of Multidrug Resistance: Synthesis, Pharmacological Activity, and Structure-Activity Relationships.

ChemInform ◽  
2010 ◽  
Vol 30 (23) ◽  
pp. no-no
Author(s):  
Jacques Ferte ◽  
Jean-Marc Kuehnel ◽  
Genevieve Chapuis ◽  
Yves Rolland ◽  
Guy Lewin ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Pharmacological Activity ◽  
Structure Activity Relationships ◽  
Structure Activity

Quinolin-2-one-pyrimidine Hybrids Acting as Potent Reversal Agents on the P-gp-mediated Multidrug Resistance: Insights into Structure-activity Relationships and the Binding Mode

2021 ◽  
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

Abstract P-gp-associated multidrug resistance (MDR) 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 moiety 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.

Flavonoid Dimers as Bivalent Modulators for P-Glycoprotein-Based Multidrug Resistance: Structure-Activity Relationships

ChemMedChem ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 594-614 ◽  
Author(s):  
Kin-Fai Chan ◽  
Yunzhe Zhao ◽  
Toby W. S. Chow ◽  
Clare S. W. Yan ◽  
Dik Lung Ma ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
P Glycoprotein ◽  
Resistance Structure

Jatrophanes as promising multidrug resistance modulators: Advances of structure–activity relationships

Fitoterapia ◽  
2018 ◽  
Vol 127 ◽  
pp. 138-145 ◽  
Author(s):  
Jun Li ◽  
Wen-qiong Wang ◽  
Shuai Tang ◽  
Wei-bin Song ◽  
Li-jiang Xuan
Keyword(s):  
Multidrug Resistance ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Resistance Modulators

Synthesis and structure–activity relationships of taxuyunnanine C derivatives as multidrug resistance modulator in MDR cancer cells

2007 ◽  
Vol 17 (13) ◽  
pp. 3722-3728 ◽  
Author(s):  
Toshiaki Hasegawa ◽  
Jiao Bai ◽  
Jungui Dai ◽  
Liming Bai ◽  
Junichi Sakai ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Cells ◽  
Structure Activity Relationships ◽  
Structure Activity
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