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Planta Med 2023; 89(13): 1236-1249
DOI: 10.1055/a-1770-7581
Natural Product Chemistry and Analytical Studies
Original Papers

Molecular Descriptors and QSAR Models for Sedative Activity of Sesquiterpenes Administered to Mice via Inhalation

Godfried Dougnon 
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
,
Michiho Ito
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
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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

Supporting Information

    A complete list of the initial 114 sesquiterpene compounds with name, structure, and physiochemical properties is available as Supporting Information.

  • Supporting Information


Publication History

Received: 16 November 2021

Accepted after revision: 11 February 2022

Accepted Manuscript online:
14 February 2022

Article published online:
03 July 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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