QSAR analysis on Spodoptera litura antifeedant activities for flavone derivatives

• Published in: The Science of the total environment 2009-12, Vol.408 (2), p.277-285
• Main Authors: Duchowicz, Pablo R., Goodarzi, Mohammad, Ocsachoque, Marco A., Romanelli, Gustavo P., Ortiz, Erlinda del V., Autino, Juan. C., Bennardi, Daniel O., Ruiz, Diego M., Castro, Eduardo A.
• Format: Article
• Language: English
• Subjects: 3-coumarones; Acceptability; Animal, plant and microbial ecology; Animals; Antifeedant activity; antifeeding activity; Applied ecology; aurones; Benzofurans - chemistry; Benzofurans - pharmacology; Biological; Biological and medical sciences; chromones; Chromones - chemistry; Chromones - pharmacology; Derivatives; Ecotoxicology, biological effects of pollution; Feeding; Feeding Behavior - drug effects; Flavone derivatives; flavones; Flavones - chemistry; Flavones - pharmacology; Fundamental and applied biological sciences. Psychology; General aspects; insect repellents; Insect Repellents - pharmacology; Mathematical models; Molecular structure; pED50; QSAR models; QSAR Theory; Quantitative Structure-Activity Relationship; quantitative structure-activity relationships; Regression; regression analysis; Replacement Method; Spodoptera - drug effects; Spodoptera litura
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2009.09.041

We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED 50 feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure–Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds. After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure–activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-(α-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED 50 = 1.162.