Optimization of a Tertiary Alcohol Series of Phosphodiesterase-4 (PDE4) Inhibitors:  Structure−Activity Relationship Related to PDE4 Inhibition and Human Ether-a-go-go Related Gene Potassium Channel Binding Affinity

2003 ◽  
Vol 46 (12) ◽  
pp. 2413-2426 ◽  
Author(s):  
Richard W. Friesen ◽  
Yves Ducharme ◽  
Richard G. Ball ◽  
Marc Blouin ◽  
Louise Boulet ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Binding Affinity ◽  
Structure Activity Relationship ◽  
Tertiary Alcohol ◽  
Activity Relationship ◽  
Related Gene ◽  
Phosphodiesterase 4 ◽  
Structure Activity

Structure-Activity Relationship of Dicoumarol Derivatives as anti- Staphylococcus aureus (Staph Infection) Agents

2019 ◽  
Vol 17 (2) ◽  
pp. 93-98
Author(s):  
Nidaa Rasheed ◽  
Natalie J. Galant ◽  
Imre G. Csizmadia
Keyword(s):  
Staphylococcus Aureus ◽  
Binding Affinity ◽  
Inverse Correlation ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Qsar Studies ◽  
Structure Activity ◽  
Aromatic Donor ◽  
Direct Binding

<P>Introduction: Staph infection, caused by a bacterium known as Staphylococcus aureus, results in a range of diseases from cellulitis to meningitis. Dicoumarol compounds are now emerging as new anti-Staph infection agents as they possess a different chemical structure than compounds used in previous treatments, in order to combat antibiotic-resistant strains. However, it is unclear how such chemical modulations to the dicoumarol backbone structure achieve higher drug performance. Methods: The following review analyzed various quantitative structure-activity relationship (QSAR) studies on dicoumarol compounds and compared them against the corresponding minimum inhibitory concentration and binding affinity values. Results: Compared to the antimicrobial activity, the dicoumarol derivatives with electron withdrawing substituents, CL, NO2, and CF3 showed an inverse correlation; whereas, the opposite was observed with electron donating compounds such as OH, OMe, and amine groups. Based on the interactions of dicoumarol at the active site, an “aromatic donor-acceptor” relationship was proposed as the method of action for this drug. Furthermore, substituent positioning on the benzene ring was found to exert a greater effect on the binding affinity, speculating that the mechanism of action is two characteristics based, needing, both, the proper aromatic pi-pi interaction for stabilization and direct binding to the OH group in the Tyrosine residue, affected by the steric hindrance. Conclusion: This foundational review can enhance productivity sought by the pharmaceutical agency to use combinational chemistry to increase the efficiency to discover new hits in the synthesis of dicoumarol drugs against Staph infection.</P>

Sign in / Sign up

Export Citation Format

Share Document