RP TLC data in correlation studies with in silico pharmacokinetic properties of benzimidazole and benztriazole derivatives

Eur J Pharm Sci. 2013 Apr 11;49(1):10-7. doi: 10.1016/j.ejps.2013.01.018. Epub 2013 Feb 9.

Abstract

Reversed-phase thin-layer chromatographic (RP TLC) retention constants for a newly designed series benzimidazole/benztriazole with expected biological activity were determined as parameters of their lipophilicity and this series was recognized as congeneric. Pharmacokinetic descriptors of the compounds investigated were calculated in silico with the use of the established drug design software. The bioactivity descriptors, which are assumed to predicted drug absorption, distribution, metabolism, elimination and toxicity (ADMETox) in humans, were correlated with retention constants and good statistical parameters were obtained. Multiple regression analysis which was introduced suggested that the absorption through different epithelial membranes (intestinal, blood-brain or erythrocyte membrane) and distribution process depend on retention constants (as measure of lipophilicty) and total polar surface area and molar weight/volume of the analyte. Finally, the compounds with halogen substituent (compounds A4/A7 and A5/A8 in Table 1), were suggested as the best drug candidates, because of their predicted proper pharmacokinetics and have been proposed for further biological tests.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzimidazoles / chemistry
  • Benzimidazoles / pharmacokinetics*
  • Chromatography, Reverse-Phase
  • Chromatography, Thin Layer
  • Computer Simulation
  • Drug Design
  • Linear Models
  • Software
  • Triazoles / chemistry
  • Triazoles / pharmacokinetics*

Substances

  • Benzimidazoles
  • Triazoles
  • benzimidazole