Exploratory Studies on Diterpenoids and Other Constituents From the Root Bark of Croton oligandrum Pierre Ex Hutch (Euphorbiaceae) via Biological Activities and In Silico Evaluations.

A new ferulic acid ester named ferulicrotonoate was isolated from the root bark of Croton oligandrum with 14 known compounds. Among the isolated compounds, trachyloban-15α-18-diol exhibited the most significant bioactivity, with metal chelating and free radical scavenging activities of 3.79 ± 0.67 and 3.88 ± 1.03 µg/mL, respectively. These quantitative results underscore the potential of Croton species as a source of potent antioxidants. The reducing power of crotozambefuran A was 43.30 ± 0.01 µg/mL. Trachinodiol and sitoindoside I demonstrated the lowest MIC value of 64 µg/mL against E. coli. The 3-O-acetylaleuritolic acid was the most effective against B. cereus (<1). The binding affinity and constant of Sitoindoside I for BSA are -7.90 kcal/mol and 1.59 µM, respectively. ADMET prediction suggested favorable pharmacokinetic properties for trachyloban-15α-18-diol, including high gastrointestinal absorption and potential blood-brain barrier permeability. Trachyloban-15a-18-diol > β-sitosterol palmitate > cytoindosit I > 4-hydroxy-3-methoxybenzaldehyde is the sequence from the most to the least stable molecules. Trachyloban-15α-18-diol is nucleophilic and has the lowest electrophilicity index value (0.043 eV). The in silico studies, including molecular docking with BSA and ADMET profiling, were conducted to evaluate the pharmacokinetic behavior and transport potential of the isolated compounds rather than their direct enzymatic inhibition mechanisms. These findings indicate that trachyloban-15α-18-diol may warrant further investigation as a bioactive lead compound.