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

• Main Authors: Inoue, Rinnalyn N., Nonato, Maybel M., Janairo, Jose Isagani B., Yu, Derrick Ethelbhert C.
• Format: text
• Published: Animo Repository 2012
• Subjects: NF-kappa B (DNA-binding protein); Enzyme inhibitors; Metabolites; Diterpenes; Atomic, Molecular and Optical Physics
• Online Access: https://animorepository.dlsu.edu.ph/faculty_research/6599
• Institution: De La Salle University

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.