Rational Design of Aspergillusidone A-F Isolated from Marine-Derived Fungus Aspergillus unguis as New PknG Inhibitors
Aspergillusidone A-F were isolated from marine-derived fungus Aspergillus unguis. Several inhibitory activities
against potential target of these compounds were reported. To help biomedical science to find new inhibitory activity of
Aspergillusidone A-F bioactive compounds against new potential targets, we aim to find new inhibitory activity against
tuberculosis, the problem infection disease in Thailand. Molecular docking calculations was employed to model
Aspergillusidone A-F complexed with M. tuberculosis PknG. The obtained results revealed that Aspergillusidone A was
strongest bound to ATP binding site of M. tuberculosis PknG with docking score of -9.08 kcal/mol. Based on MD simulations
followed by MM-GBSA interaction energy calculations, the crucial interactions of this compound are hydrogen bond
interactions between Aspergillusidone A and Lys181, Glu233, Val235 and Arg242. In addition, molecular behavior
Aspergillusidone A/PknG complexed was provided the key information to develop as highly specific PknG inhibitors.
Therefore, the obtained results from this study guide to design the new potential bioactive compounds and biological assay
evaluation against PknG and M. tuberculosis cell to find new anti-tuberculosis agents.
Index Terms — Aspergillusidone, biomedical science, PknG, tuberculosis, molecular modeling.