Development of structure-activity modelling of carboxamides compounds for Aedes Aegypti repellents

Abstract

Recently, research has been critically focused on finding new compounds with antirepellent activity due to the rising of new types of mosquito-borne diseases. Mosquito repellents are the safer and cleaner alternative to fight the anthropods from bitten human skins, hence reduce the spread of diseases. This study investigated the relationships between biological activity and structure of carboxamides by using Quantitative Structure-Activity Relationship (QSAR) analysis. The data set used in this study comprised of 40 carboxamide compounds taken from the literature with their activities expressed as log PT (protection time). These compounds were split into training set for model building and test set for external validation using activity-based ranking method. The training set contained approximately 75% of the compounds while the remaining compounds were then used as the validation set to verify the accuracy of the model. DRAGON software was employed to generate molecular descriptors. The important relevant descriptors were further selected and reduced by using Genetic Algorithm (GA) as variable selection method. Two QSAR models were developed by combining GA method with two different modelling techniques that are multiple linear regressions (MLR) and partial least square (PLS). All the models are robust with good correlation coefficient (r2) greater than 0.6 and external validation r2test more than 0.5. Statistics of the GA-MLR model are r2 = 0.779 and r2test = 0.646. Whereas, the second model generated from GA and PLS shows good r2 with value of 0.775 and r2test = 0.563. These results could be useful in finding new, safe, and more effective repellents against Aedes Aegypti in a short time by providing guidance for further laboratory work as well as prediction of external compounds and help to understand the factors affecting their activity.