QSTR with extended topochemical atom (ETA) indices. 14. QSAR modeling of toxicity of aromatic aldehydes to Tetrahymena pyriformis.
Aldehydes are a toxic class of chemicals causing severe health hazards. In this background, quantitative structure-toxicity relationship (QSTR) models have been developed in the present study using Extended Topochemical Atom (ETA) indices for a large group of 77 aromatic aldehydes for their acute toxicity against the protozoan ciliate Tetrahymena pyriformis. The ETA models have been compared with those developed using various non-ETA topological indices. Attempt was also made to include the n-octanol/water partition coefficient (logK(o/w)) as an additional descriptor considering the importance of hydrophobicity in toxicity prediction. Thirty different models were developed using different chemometric tools. All the models have been validated using internal validation and external validation techniques. The statistical quality of the ETA models was found to be comparable to that of the non-ETA models. The ETA models have shown the important effects of steric bulk, lipophilicity, presence of electronegative atom containing substituents and functionality of the aldehydic oxygen to the toxicity of the aldehydes. The best ETA model (without using logK(o/w)) shows encouraging statistical quality (Q(int)(2)=0.709,Q(ext)(2)=0.744). It is interesting to note that some of the topological models reported here are better in statistical quality than previously reported models using quantum chemical descriptors.
Roy
Kunal
K
Drug Theoretics and Cheminformatics Laboratory, Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India. kunalroy_in@yahoo.com
Das
Rudra Narayan
RN
D000447:Aldehydes / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013769:Tetrahymena pyriformis / Q000187:drug effects*
D000447:Aldehydes; D000981:Antiprotozoal Agents; D006841:Hydrocarbons, Aromatic