The Three Dimensional Quantitative Structure Activity Relationships (3D-QSAR) and Docking Studies of Curcumin Derivatives as Androgen Receptor Antagonists

Fatty Acid Amide Hydrolase (FAAH) is one of the main enzymes responsible for endocannabinoid metabolism. Inhibition of FAAH increases endogenous levels of fatty acid ethanolamides such as anandamide (AEA) and thus consitutes an indirect strategy that can be used to modulate endocannabinoid tone. In the present work, we present a three-dimensional quantitative structure-activity relationships/comparative molecular similarity indices analysis (3D-QSAR/CoMSIA) study on a series of 90 reported irreversible inhibitors of FAAH sharing a piperazine-carboxamide scaffold. The model obtained was extensively validated (q2 = 0.734; r2 = 0.966; r2m = 0.723). Finally, based on the information derived from the contour maps we designed a series of 10 new compounds with high predicted FAAH inhibition (predicted pIC50 of the best-proposed compounds = 12.196; 12.416).

Download Full-text

Towards further Understanding the Structural Requirements of Combretastatin- like Chalcones as Inhibitors of Microtubule Polymerization

Current Computer - Aided Drug Design ◽

10.2174/1573409915666181221114107 ◽

2020 ◽

Vol 16 (2) ◽

pp. 155-166

Author(s):

Naveen Dhingra ◽

Anand Kar ◽

Rajesh Sharma

Keyword(s):

Three Dimensional ◽

3D Qsar ◽

Docking Study ◽

Structure Activity Relationship ◽

Docking Studies ◽

Activity Relationship ◽

Structural Requirement ◽

Ligand Interaction ◽

Microtubule Polymerization ◽

Structure Activity

Background: Microtubules are dynamic filamentous cytoskeletal structures which play several key roles in cell proliferation and trafficking. They are supposed to contribute in the development of important therapeutic targeting tumor cells. Chalcones are important group of natural compounds abundantly found in fruits & vegetables that are known to possess anticancer activity. We have used QSAR and docking studies to understand the structural requirement of chalcones for understanding the mechanism of microtubule polymerization inhibition. Methods: Three dimensional (3D) QSAR (CoMFA and CoMSIA), pharmacophore mapping and molecular docking studies were performed for the generation of structure activity relationship of combretastatin-like chalcones through statistical models and contour maps. Results: Structure activity relationship revealed that substitution of electrostatic, steric and donor groups may enhance the biological activity of compounds as inhibitors of microtubule polymerization. From the docking study, it was clear that compounds bind at the active site of tubulin protein. Conclusion: The given strategies of modelling could be an encouraging way for designing more potent compounds as well as for the elucidation of protein-ligand interaction.

Download Full-text

Molecular Shape Descriptors. 2. Quantitative Structure-Activity Relationships Based Upon Three-Dimensional Molecular Shape Descriptor

Zeitschrift für Naturforschung A ◽

10.1515/zna-1985-1107 ◽

1985 ◽

Vol 40 (11) ◽

pp. 1114-1120

Author(s):

loan Motoc ◽

Garland R. Marshall

Keyword(s):

Enzyme Inhibitor ◽

Three Dimensional ◽

Shape Descriptor ◽

Molecular Shape ◽

Quantitative Structure Activity Relationship ◽

Quantitative Structure ◽

E Coli ◽

Interactional Pattern ◽

Structure Activity ◽

Quantitative Structure Activity Relationships

A methodology to incorporate the three-dimensional molecular shape descriptor (3 D-MSD) into a quantitative structure-activity relationship is discussed in detail. The 3 D-MSD is calculated and correlated with Kiapp values for a set of 2,4-diamino-5-benzylpyrimidines which inhibit E. coli DHFR. The correlation (n = 22, r = 0.95, s = 0.214, F = 55.10) indicates that the polarization interaction dominates the enzyme-inhibitor interactional pattern.

Download Full-text