Computational ligand-based molecular analysis of kaurenoic acid and kaurane diterpene derivatives as NF-kB pathway inhibitors

College

College of Science

Department/Unit

Physics

Document Type

Article

Source Title

Journal of Computational Methods in Molecular Design

Volume

2

Issue

3

First Page

92

Last Page

98

Publication Date

2012

Abstract

Kaurenoic acid derivatives and kaurane diterpenes are known to be inhibitors of the NF-kB pathway wherein both compounds share the same tetracyclic structure. Despite sharing close structural homology, Kaurenoic acid derivatives exert their activity through IKK inhibition whereas Kaurane diterpenes inhibit the p50 protein. Thus, a ligand-based similarity analysis was conducted in order to explain the observed target differences between the two sets of compounds through the calculation of chemical descriptors derived using the AM1 Hamiltonian. The calculated molecular descriptors for each set of molecules were then statistically compared in order to determine which among them may explain the observed target difference. Results indicated that size, hydrophobicity, and thermodynamic variables associated with binding were the points of differentiation for the observed target differences between the two sets of compounds.

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Disciplines

Atomic, Molecular and Optical Physics

Keywords

NF-kappa B (DNA-binding protein); Enzyme inhibitors; Metabolites; Diterpenes

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