Abstract
Essential oils are often utilized for therapeutic purposes and are composed of complex structural molecules, including sesquiterpenes, with high molecular weight and potential for
stereochemistry. A detailed study on the properties of selected sesquiterpenes was conducted as part of a broader investigation on the effects of sesquiterpenes on the central nervous
system. A set of 18 sesquiterpenes, rigorously selected from an original list of 114, was divided into 2 groups i.e., the training and test sets, with each containing 9 compounds. The
training set was evaluated for the sedative activity in mice through inhalation, and all compounds were sedatives at any dose in the range of 4 × 10−4–4 × 10−2 mg/cage,
except for curzerene. Molecular determinants of the sedative activities of sesquiterpenes were evaluated using quantitative structure–activity relationship (QSAR) and structure–activity
relationship (SAR) analyses. An additional test set of six compounds obtained from the literature was utilized for validating the QSAR model. The parental carbonyl cation and an
oxygen-containing groups are possible determinants of sedative activity. The QSAR study using multiple regression models could reasonably predict the sedative activity of sesquiterpenes with
statistical parameters such as the correlation coefficient r2 = 0.82 > 0.6 and q2
LOO = 0.71 > 0.5 obtained using the leave-one-out cross-validation
technique. Molar refractivity and the number of hydrogen bond acceptors were statistically important in predicting the activities. The present study could help predict the sedative activity
of additional sesquiterpenes, thus accelerating the process of drug development.
Key words
ADMET - QSAR - essential oil - sesquiterpene - sedative - inhalation
