Abstract
Quantitative structure-activity relationships (QSARs) for benz[a]anthracene (BA)mutagens using 73 descriptors were searched. The mutagenicity data was obtained fromAmes assays for Mycobacterium vanbaalenii, Mycobacterium gilvum and Mycobacteriumflavescens strains. These data were fitted using a mutagenicity-cytotoxicity competitionmodel which defines the mutagenic potencies of BA metabolites, and include oxides,phenols, quinones, and dihydrodiols. The QSAR equations were derived using the moleculardescriptor set (charged partial surface area, spatial, thermodynamic and electronicdescriptors) and semi-empirical energetic and charge descriptors. Genetic functionapproximation was used to reduce and fit independent variables, including linear- andquadratic-based functions. Multiple QSAR equations were generated and a separate QSARequation was chosen and evaluated for each strain using conventional r2, F-test, and cross-validated r2. Each strain exhibited its own characteristic descriptors.
Highlights
Benz[a]anthracene (BA) and its metabolitic products which are metabolically activated and are both mutagenic and carcinogenic polycyclic aromatic compounds (PAH) include BA-oxides, -phenols, quinones, -dihydrodiols and -diolepoxides [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]
Since the mutagenicity of PAH metabolites relies on both metabolic activation and their ability to intercalate and bind DNA, performing a quantitative structure-activity relationships (QSARs) study that relates the mutagenicity of these metabolites to physicochemical parameters such as potential energy and electronic charge might provide statistically reliable insights such as providing quantitative information on the mutagenic mechanisms of PAH by bay-region theory and activities of free radical intermediates, as well as enable exploration of various structural features
In the present work we have considered the mutagenicity data for 29 BA-oxides, -phenols, quinones, and -dihydrodiols from a data set presented by previous studies [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]
Summary
Benz[a]anthracene (BA) and its metabolitic products which are metabolically activated and are both mutagenic and carcinogenic polycyclic aromatic compounds (PAH) include BA-oxides, -phenols, quinones, -dihydrodiols and -diolepoxides [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Given that the GFA will generate multiple models, each QSAR equation must be evaluated using an Ftest, in order to determine significance and correlation coefficient to activity. The following correlation values were obtained for the three mutagenic activity data sets: 0.8509 (MV and MG); 0.8972 (MV and MF); and 0.8814 (MG and MF).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
