In vitro screening and chemometrics analysis on a series of azole derivatives with fungicide activity against moniliophthora perniciosa

Abstract

Moniliophthora perniciosa, o agente causal da vassoura-de-bruxa do cacaueiro, diminuiu significativamente a produção de cacau, especialmente no estado da Bahia, a maior região produtora de cacau do continente americano. As formas de controle desenvolvidas até o momento têm baixa eficiência. Derivados de azol são ativos tanto in vitro quanto in loco contra M. perniciosa, porém não há um estudo sistemático sobre a atividade dos azóis contra este fitopatogeno. Dados biológicos, obtidos em um ensaio padronizado, foram utilizados para criação de modelos quimiométricos, que destacam características físico e estruturais importantes para a atividade fungicida de derivados de azol frente a M. perniciosa. De acordo com os modelos de PCA e SIMCA, características eletrônicas, representadas pelos descritores BEHe3 e JGI4, paralelamente à possibilidadde de realizar ligações de H e ausência de átomos de cloro, distantes de 6-8 ligações dos nitrogênios do anel azólico, parecem contribuir para atividade fungicida dos compostos estudados Moniliophthora perniciosa, the causal agent of witches' broom disease in Theobroma cacao, significantly decreased cacao production, especially in Bahia State, the largest cocoa producing of the American continent. Control programs developed so far have low efficiency. Azole derivatives are active both in vitro and in loco against M. perniciosa, however there is no comprehensive study on the activity of azoles against this phytopatogen. Standardized in vitro biological data were employed to develop supervised and unsupervised chemometric models that highlight physicochemical and structural features that are crucial for azole's fungicidal activity against M. perniciosa. Thus, PCA and SIMCA models suggest that electronegativity (BEHe3) and dipolar moment (JGI4), as well as H-bonding to M. pernciosa's lanosterol 14α-desmethylase active site and lack of Cl atoms 6 to 8 bonds from the azole's nitrogen atoms play a major role to azoles' fungicide activity.

In Silico Prediction of O6-Methylguanine-DNA Methyltransferase Inhibitory Potency of Base Analogs with QSAR and Machine Learning Methods

“…Compounds with increased MGMT inhibitory activities were tended to have high dipole moment (JGI4 values). The importance of charge transfer has already been reported in other study [ 26 ]. SpPosA_B(p) means normalized spectral positive sum from Burden matrix weighted by polarizability, is another important variable positively correlates with the increased MGMT inhibition of base analogs.…”

How do water matrices influence QSPR models in wastewater treatment?–A case study on the sonolytic elimination of phenol derivates

“…It therefore measures the charge transfer between pairs of atoms separated by four bonds, and consequently, the global charge transfer in the molecule (e.g. dipol moment) [40,41]. The positive coefficient for example in the QSPR model NaCl/Glucose (Table 2) indicates, that a specific charge distribution enhances the sonolytic degradability of a molecule.…”

Analysis of the ergosterol biosynthesis pathway cloning, molecular characterization and phylogeny of lanosterol 14α-demethylase (ERG11) gene of Moniliophthora perniciosa

“…The action of azole-group antifungals has created new perspectives for controlling witches’ broom in cocoa trees and has highlighted the importance of analyzing ergosterol biosynthesis in M. perniciosa in order to develop specific inhibitors of this pathway ( McQuilken and Rudgard, 1988 ; Mota et al , 2010 ). To accomplish this, it is essential to study the development of the disease from molecular and biochemical perspectives.…”