New neuroprotective sesquiterpene lactate esters from carotol biotransformation

Abstract

Biotransformation of carotol (1), the major sesquiterpenoid of carrot fruit essential oil, by Rhizopus oryzae yielded two new lactate derivatives: 9α-hydroxydaucol-9-lactate (2) and 9α-hydroxydaucol-3,9-dilactate (3). The structures of 1-3 were characterized by 1 & 2D NMR spectroscopy in conjunction with HR-ESIMS. Cholinergic deficiency and neuroinflammation are key detrimental processes involved in the etiology of Alzheimer's disease (AD). This study demonstrated that compounds 1-3 in addition to the essential oil showed considerable in-vitro inhibition of cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and butyrylcholinesterase (BChE). Metabolite 2 showed improved inhibitory activities (9.03, 0.56, and 0.64 μM) against COX-2, 5-LOX, and BChE enzymes, compared to the parent compound, carotol 1 (82.57, 2.11, and 0.74 μM, respectively). The results were correlated to the in-silico binding interactions with the proteins of these enzymes by molecular docking. Carrot essential oil and carotol derivatives are suggested by this study as a potential treatment for neurodegenerative disease associated with neuroinflammation.