QSARs for Toxicity of DDT-Type Analogs Using Neural Network

Abstract

Structure-toxicity relationships for 120 insecticidal DDT-type molecules including diaryl nitropropanes (Prolan analogs), diaryl trichloroethane and other DDT isosters, collected from different literature sources, to Musca domestica. were analysed by regression analysis (RA) and a neural network model (NN). The steric factors are extremely important to the toxicity of all the DDT-type analogs. The lipophilicity is also important for the groups, because it facilitates delivery of these neurotoxicants to the site of action in the nerve. On the basis of training results, the NNs proved to give better results than a regression analysis technique and the most accurate predictions. To describe the role of each of the descriptors we suggested a new method based upon the estimation of the connection weights, the identification and the rationalisation of the residuals.

QSAR analyses of DDT analogues and theirin silicovalidation using molecular docking study against voltage-gated sodium channel ofAnopheles funestus

“…The descriptor 'SKMostHydrophobicHydrophilicDistance' signifies distance between most hydrophobic and hydrophilic point on the vdW surface, while the descriptor 'PolarSurfaceAreaIncludingPandS' signifies total polar surface area including phosphorous and sulphur. These two descriptors justified the significance of the lipophilic surface on the molecule as reported earlier [13]. The descriptor 'SsssCHE-index' defines electro-topological state indices for a number of -CH groups connected with three single bonds.…”

“…While studying the SAR for organochlorine and pyrethroid pesticides, lipophilicity was found to be important for all the groups because it facilitates the delivery of these neurotoxicants to the site of action in the nerve [12]. The lipophilicity and steric factors have been reported important to the activity of all the DDT-type analogues [13]. During a comparative study of toxicity of DDT and its analogues on susceptible and resistant houseflies and mosquitoes, compounds were found to be highly effective against DDT-resistant flies and mosquitoes by blocking the detoxification mechanism by o-chlorination and α-fluorination [14].…”

Computer Aided Pesticide Design: A Rational Tool for Supplementing DDT Lacunae

“…Existing structure-activity data provides insights into mechanism or identifying an alternative mechanism of action, identifying important structural characteristics, suggesting new design strategies and synthetic targets, narrowing the dose range for a planned assay, assisting in generation of new hypotheses to guide further research, and revealing chemicals that deviate from the QSAR model. Several successful QSARs have attracted the medicinal chemists to investigate the relationship of structural properties with biological activity [45][46][47] . QSAR (Quantitative Structure Activity Relationship) relates the biological activity of molecule to some selected features of their physicochemical structure by means of a statistical tool.…”