Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3--Tirucallane Triterpenoids Meliadubins A and B from Cav. Barks with ChemGPS-NP and In Silico Prediction

Two new rearranged 2,3--tirucallane triterpenoids, meliadubins A () and B (), along with four known compounds, -, were isolated from the barks of Cav. Compound exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC at 5.54 ± 0.36 μM). It bound to active sites of a human inducible nitric oxide synthase (3E7G) through interactions with the residues of GLU377 and PRO350, which may benefit in reducing the neutrophilic inflammation effect. The ChemGPS-NP interpretation combined with bioactivity assay and in silico prediction results suggested to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds and showed remarkable inhibition against the rice pathogenic fungus in a dose-dependent manner with IC values of 137.20 ± 9.55 and 182.50 ± 18.27 μM, respectively. Both and displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of and in the ChemGPS-NP physical-chemical property space indicated that both compounds are quite different compared to all members of a selected set of reference compounds. In light of demonstrated biological activity and in silico prediction experiments, both compounds possibly exhibited activity against phytopathogenic fungi via a novel mode of action.