Application of planar chromatographic descriptors to the prediction of physicochemical properties and biological activity of compounds

ABSTRACT

A review of applications of thin layer chromatography (TLC) in drug discovery is given. TLC is presented as a tool to determine the solutes physicochemical properties (lipophilicity, dissociation constant, water solubility) and to predict the interactions of drugs with biomembranes, blood-brain barrier permeability, plasma protein binding, volume of distribution, gastric and skin absorption. Results of modeling based on thin layer chromatographic descriptors are correlated with those obtained by other in vitro techniques used to study drug bioavailability (caco-2 cells, Madin-Darby canine kidney cells, liposome partition). Modified stationary phases used to study receptor-drug interactions are also discussed. Some new trends and ideas in TLC chromatography and its applications in the drug discovery process are presented.

GRAPHICAL ABSTRACT

KEYWORDS:

• Blood-brain barrier
• gastric bioavailability
• plasma protein binding
• receptor affinity
• skin permeability
• TLC chromatography

Conflict of interest

The Authors declare that there is no conflict of interest related to the publication of this manuscript.

Abbreviations

SOTLC- salting out chromatography; MTLC – micellar thin layer chromatography; HD – hydrogen bond donor; HA – hydrogen bond acceptor; E_T – total energy; H_F – heat of formation; E_HOMO, E_LUMO – energy of the highest occupied (lowest unoccupied) molecular orbital, E_B - binding energy, Q_N - net atomic charge on atom N, MR - molar refractivity; (T)PSA – (total) polar surface area, S_a – grid surface area, MW – molecular weight; SC- stratum corneum; BBB – blood-brain barrier, HIA – human intestinal absorption; PPB – plasma protein binding; V_D – volume of distribution; V – van der Waals molar volume; DM – dipol moment; DELS – molecular electrotopological variation; TPSA(NO) – topological polar surface area; F06[N-O] – frequency of N-O at the topological distance 6, O-057 – phenol, enol, carboxyl OH group; MR – molar refractivity; EP - electrostatic potential.

Acknowledgements

Special thanks are due to Professor Elżbieta Brzezińska for her constant support and encouragement.

Additional information

Funding

This work was supported by Medical University of Lodz, Poland: [Grant number 503/3-016-03/503-31-001].