Isolation optimisation, synthesis, molecular docking and in silico ADMET studies of lantadene a and its derivatives

A simple and economical method was developed for the extraction and isolation of pentacyclic triterpenoid lantadene A from the leaves of Lantana camara. The lantadene A displays significant anti-inflammatory and anticancer properties via the inhibition of IKK-mediated NF-κB protein. Therefore, the derivatives of lantadene A were synthesised to further optimise the pharmacophore for anti-inflammatory and anticancer activities. The synthesised compounds were docked into the active site of IKK to find the most potent inhibitor of IKK. Molecular docking studies revealed that 3β,22β-diisobutyl substituted lantadene derivative (10) binds to the IKK protein with the highest affinity. Furthermore, in the in silico ADMET studies, the lead IKK inhibitor (10) was found to be Ames non-toxic, non-carcinogen, and a weak inhibitor of hERG.[Figure: see text].