Original scientific paper

Quantitative Structure-activity Relationship Modeling of Mosquito Repellents Using Calculated Descriptors

Ramanathan Natarajan ; Center for Water and the Environment, Natural Resources Research Institute, University of Minnesota Duluth, USA
Subhash C. Basak ; Center for Water and the Environment, Natural Resources Research Institute, University of Minnesota Duluth, USA
Denise Mills ; Center for Water and the Environment, Natural Resources Research Institute, University of Minnesota Duluth, Duluth, MN, USA
Jessica J. Kraker ; School of Statistics, University of Minnesota Twin Cities, Minneapolis, MN, USA
Douglas M. Hawkins ; School of Statistics, University of Minnesota Twin Cities, Minneapolis, MN, USA

Abstract

Quantitative structure-activity relationship (QSAR) modeling of 40 DEET-related mosquito repellents
was carried out using calculated molecular descriptors. When the four different classes
of descriptors (topochemical, topostructural, geometrical and quantum chemical) were used in
a hierarchical fashion, topochemical descriptors were found to explain much of the variance in
the data and this indicated the importance of the chemical nature of the atoms and groups towards
repellency of these compounds. Ridge regression (RR) outperformed partial least square
regression (PLS) and principal component regression (PCR). We also used descriptor thinning
via a modified Gram-Schmidt algorithm prior to ridge regression. This resulted in a four-parameter
model with a 20-fold cross-validated R2 of 0.734. The q2 (R2cv) reported here is the
"true-q2" because the descriptor thinning was embedded within the cross-validation step. Inclusion
of any calculated physicochemical property (secondary descriptor) did not result in improvement
of the models built with the calculated molecular descriptors (primary descriptors).
This result has great implications in the QSAR assisted design of new mosquito repellents because
calculation of the primary descriptors does not require any input other than the molecular
structure.

Keywords

DEET; mosquito repellents; QSAR; topological indices

Hrčak ID:

28499

URI

https://hrcak.srce.hr/28499

Publication date:

30.6.2008.

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