QSAR modelling and structural aspects concerning synthetic heterocycles with larvicidal activity against Aedes aegypti
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ORIGINAL RESEARCH
QSAR modelling and structural aspects concerning synthetic heterocycles with larvicidal activity against Aedes aegypti João Pedro Agra Gomes 1 & Eduard David Simões Mourão 2 & Janaina Versiani dos Anjos 3 & Edilson Beserra de Alencar Filho 1,2,4 Received: 28 May 2020 / Accepted: 16 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract In this paper, we present a quantitative structure–activity relationships modelling for two series of heterocyclic synthetic compounds with larvicidal activity against Aedes aegypti. This is a vector of important disease around the tropical countries as dengue, zika, and chikungunya. The compounds corresponded to a set of 21 girgensohnine natural product analogues, containing an acetonitrile moiety, and 35 synthetic oxadiazoles and isoxazoles. The activities were expressed by IC50 values in direct acetylcholinesterase inhibition (acetonitriles), as well as LC50 in the observation of the larvae death (oxadiazoles/isoxazoles). Robust and predictive MLR (multiple linear regression) models were obtained after a variable selection procedure, using the OPS (ordered predictors selector) algorithm and Dragon descriptors. We highlighted important molecular descriptors related to the activity of each class, in order to predict molecular modifications for the synthesis of new and more active compounds. We also provided an initial path for qualitative understanding of the activity spectrum in each of the class studied herein. Keywords QSAR . Dragondescriptors . Larvicidal activity inAedes aegypti . Girgensohnine analogues . Oxadiazoles . Isoxazoles
Introduction The arboviruses dengue, chikungunya, and zika are important public health problems around the world [1]. The main
transmitting vector of those arboviruses is the Aedes aegypti mosquito, and it can be considered “the most dangerous animal in the world” [1, 2], if we consider death rates and disease outcomes associated with the addressed conditions.
Highlights • Molecular modelling at RM1 semi-empirical Hamiltonian of 21 girgensohnine analogues, containing the acetonitrile moiety, and 35 synthetic oxadiazoles and isoxazoles, with larvicidal activity in Aedes aegypti • Calculation of Dragon® descriptors (> 5000) followed by ordered predictors selector (OPS) and systematic search algorithms • QSAR modellings considering IC50 or LC50 for the two classes of compounds against Aedes aegypti • Molecular highlights were presented, allowing the qualitative understanding, design, and prediction of future analogues. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11224-020-01597-7) contains supplementary material, which is available to authorized users. * Edilson Beserra de Alencar Filho [email protected] 1
2
College of Pharmacy, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil Postgraduate Program in Biosciences, Federal University of São Francisco Valley, Petrolina, Pernambuco, Brazil
3
Postgraduate Program
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