COMPUTER-AIDED PREDICTION COMPUTER-AIDED PREDICTION OF XENOBIOTICS TOXICITY OF XENOBIOTICS TOXICITY Reporters: Reporters: Zinchenko T.O., Nebesna Zinchenko T.O., Nebesna T.Yu. T.Yu. Scientific advisers: Scientific advisers: prof. I. S. Chekman, prof. I. S. Chekman, prof. O.P. Javorovsky prof. O.P. Javorovsky National O.O. Bogomolets Medical University National O.O. Bogomolets Medical University Department of pharmacology and clinical Department of pharmacology and clinical pharmacology pharmacology Chief of department: prof. I.S. Chekman Chief of department: prof. I.S. Chekman Department of hygiene of work Department of hygiene of work Chief of department: prof. O.P. Javorovsky Chief of department: prof. O.P. Javorovsky
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COMPUTER-AIDED PREDICTION COMPUTER-AIDED PREDICTION OF XENOBIOTICS TOXICITY OF XENOBIOTICS TOXICITY
Scientific advisers: prof. I. S. Chekman, Scientific advisers: prof. I. S. Chekman,
prof. O.P. Javorovskyprof. O.P. Javorovsky
National O.O. Bogomolets Medical UniversityNational O.O. Bogomolets Medical UniversityDepartment of pharmacology and clinical Department of pharmacology and clinical
pharmacologypharmacology Chief of department: prof. I.S. ChekmanChief of department: prof. I.S. Chekman
Department of hygiene of workDepartment of hygiene of work Chief of department: prof. O.P. JavorovskyChief of department: prof. O.P. Javorovsky
ToxicologyToxicology is the study of the adverse effects of chemicals on living organisms. It is the study of symptoms, mechanisms, treatments and detection of poisoning, especially the poisoning of people.
ToxicityToxicity is the degree to which a substance is able to damage an exposed organism.
A xenobioticA xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it.
The aim of toxicologyThe aim of toxicology testing is the safety assessment of a substance such as a
new pharmaceutical compound or a pesticide relative to a vehicle or negative control.
Toxicity kindsToxicity kinds:Toxicity kinds: Toxic effect: Specific
is a mathematical relationship between a biological activity of a molecular system and its geometric and
chemical characteristics.
OSAR applicationOSAR application:
Benefits of Using QSAR Benefits of Using QSAR ModelingModeling
No animal test data are required No need for interspecies uncertainty
factors Increased accuracy, sensitivity and
specificity over animal models (identifies chemical adverse effects not detected in animal studies)
Batch processing(prioritization of large test chemical data sets)
Reduced cost
The aim of QSAR methodThe aim of QSAR method:
analysis of a considerable quantity of descriptors to reject what practically do not influence on under investigation toxicity parameters, and to define what are bound to it.
Solution to a mathematical procedure that transforms chemical information into a numbersurface areas (polar, non-polar), dipole moment, volume
Experimental:Experimental:the result of some standardized experiment to measure a molecular attribute melting point, partition coeficients, refractive index, etc.
Types of DescriptorsTypes of Descriptors
Types of DescriptorsTypes of Descriptors Counts of features: For example HBAs, HBDs, aromatic
ring systems, substructures/fragments ( e.g. , carbonyl groups, basic nitrogens, carboxyl groups,…),etc.
Physicochemical Properties: LogP, solubility, MW, MP, BP, heat of sublimation, molar refractivity, Hammett parameters, etc.
Topological Indices: Wiener index, branching indices, kappa shape indices, electrotopological state indices, atom-pairs, topological torsions, etc.
BCUTs (3-D, 2-D, 2-T): Electrostatic, charge, and polarizability (hydrophobic).