Chromatographic descriptors in QSAR study of barbiturates

Abstract

Barbiturate derivatives were evaluated for their parameters of biological activity by applying linear regression and two multivariate methods (Cluster analysis and Principal component analysis). The lipophilicity of the studied barbiturates was determined on the modified carriers C18 in mixtures of water and four organic modifiers separately (methanol, n-propanol, acetone and tetrahydrofuran) by performing reversed phase thin layer chromatography and by applying relevant software packages. Chromatographic and computational lipophilicity of the examined barbiturates was correlated with the selected pharmacokinetic and toxicological predictors and good relationships were obtained. More concrete results were obtained by multivariate methods which showed that the polarity of the substituent has the greatest influence, and its electronic effects to a lesser extent on the tested parameters of the barbiturate derivatives. Results obtained by multivariate methods also suggest that the chromatographic retention constant, R_M⁰, shows a greater resemblance to the parameters of lipophilicity. The chromatographic parameter m, exhibits better agreement with the toxicity parameters.

Graphical Abstract

KEYWORDS:

• Barbiturate derivatives
• chemometrics
• lipophilicity
• Quantitative Structure-Activity Relationship

Acknowledgements

The authors are grateful to the team of SimulationsPlus for providing a free trial version.

Additional information

Funding

The presented results are part of the Project No. 172013 supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia.