The first investigation of the phytochemical profile of the flowers of Croton krabas led to the isolation of two new clerodane diterpenes, 6S-crotocaudin (1) and crotocaudin B (2), together with two known clerodanes, 6S-crotoeurin C (3) and isoteucvin (4). The structures and absolute configurations of isolated clerodanes were elucidated by extensive analysis of NMR spectroscopic data, mass spectrometry and ECD calculations. Compounds 1-4 demonstrated significant inhibitory activity towards acetylcholinesterase (AChE). Notably, compound 2 exhibited the strongest AChE inhibition (IC50 1.01 µM). Compounds 3 and 4 showed potent butyrylcholinesterase (BChE) inhibitory activity with IC50 values of 1.09 and 1.12 µM, respectively. The molecular docking results revealed that 2 bound to the catalytic anionic site (CAS) and peripheral anionic site (PAS) of AChE, while 3 occupied in the CAS of BChE.
Keywords: Croton krabas; acetylcholinesterase; butyrylcholinesterase; clerodane; molecular docking.