Theoretical study on the structures and pharmacokinetic evaluation of verticillane-type diterpenes from soft coral Heteroxenia ghardaqensis.

The density functional theory (DFT) method ωB97XD/6-311++G(2d, p) was applied to calculate and analyze the geometric structures, spectral properties, frontier molecular orbitals, and molecular electrostatic potentials of 14 novel verticillane-type diterpenoids isolated from the soft coral Heteroxenia ghardaqensis. Additionally, reaction index analysis was conducted using conceptual density functional theory, and the drug-likeness of these compounds was evaluated using two different pharmacokinetic prediction platforms. The results showed that the hydroxyl hydrogen, secondary amine hydrogen, carbonyl oxygen, and hydroxyl oxygen in the molecules of these compounds have relatively high reactivity. Compounds 5, 8, and 9 exhibit significant anti-inflammatory activity and have similar electronic delocalization distribution characteristics, showing good stability and excellent biological activity, among which compound 5 demonstrates more significant drug potential. For compounds 2, 8, and 12 with hepatoprotective activity, through the analysis of comprehensive pharmacokinetic parameters and molecular docking data, compound 12 is considered more suitable as a potential hepatoprotective drug.