Exploring QSAR of hydroxyphenylureas as antioxidants using physicochemical and electrotopological state atom parameters

Abstract

In the present study, free radical scavenging activity of 36 substituted hydroxyphenylurea derivatives was subjected to classical quantitative structure–activity relationship (QSAR) analyses using physicochemical (hydrophobicity and molar refractivity) and electrotopological state atom parameters. For the development of the QSAR models, statistical techniques such as stepwise multiple linear regression and genetic function approximation (GFA) were used. The developed models indicate an important contribution of the phenolic hydroxyl group of hydroxyphenylureas, apart from that of the urea moiety and piperazine nucleus of the side chain, to the free radical scavenging activity. The presence of substituents at the phenyl ring influences the electron density distribution over the phenolic ring system and modulates the activity. Hydrophobicity is found to contribute positively to the free radical scavenging activity. Based on internal validation (Q ²), external validation () and overall validation criteria (), a GFA model with spline options was found to be the best model (Q ² = 0.957,  = 0.966,  = 0.914).

Keywords:

• QSAR
• antioxidant
• hydroxyphenylurea
• GFA

Acknowledgement

C.S.G. and K.R. thankfully acknowledge the AICTE, New Delhi for the financial assistance.

Notes

^1. URL: http://sites.google.com/site/kunalroyindia/.

^2. SRETSA is a statistical software in Visual Basic, developed by S. Ray and R. Biswas and standardised using known data-sets.

^3. MINITAB is a statistical software of Minitab Inc., USA. Available at http://www.minitab.com.