Development and validation of regression-based QSAR models for quantification of contributions of molecular fragments to skin sensitization potency of diverse organic chemicals

Abstract

In our present work, we have developed regression-based QSAR models for skin sensitization potential of 51 diverse organic chemicals. The objective behind the present work is to determine the influence of different molecular features on the skin sensitizing potential of chemicals. Among several models developed, the two best ones are discussed to unveil specific information regarding the contribution of different structural and physicochemical features towards the property of skin sensitization. The QSAR models suggested that aromatic compounds are more skin sensitizing than aliphatic ones, but in the case of carbonyl compounds, aliphatic ones are more skin sensitizing than aromatic ones. Other descriptors such as LUMO and <2-Atype_H-47> signify the importance of the electrophilic and hydrophilic character respectively of the molecules for showing skin sensitizing property. Another two descriptors, <Dipole-mag-2.72> and ³χ_C also exert significant contributions towards the skin sensitization potential of the chemicals. Further, it is observed that the nitrogen atoms (nN), triple bonds (nTB) and also the fragment Al-C(=X)-Al (Atype_C38) are responsible for skin sensitizing property. All the above information provides additional support for further research involving identification of the skin sensitization potential of new chemicals.

Keywords:

• QSAR
• skin sensitization
• EC₃
• OECD
• LLNA test

Acknowledgements

This research was funded by a major research project (KR) (no. 01 (2546)/11/EMR-II) of Council of Scientific and Industrial Research, New Delhi. The authors thank the Department of Science and Technology (DST), Government of India, for awarding a Research fellowship under the INSPIRE scheme to SK. Ministry of Human Resources and Development, New Delhi, is thanked for a scholarship to AN.