Pregledni rad

https://doi.org/10.5599/admet.553

Immobilized artificial membrane chromatography: from medicinal chemistry to environmental sciences

Fotis Tsopelas orcid.org/0000-0001-6917-2028 ; Laboratory of Inorganic and Analytical Chemistry, School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou 9, 157 80 Athens, Greece.
Chrysanthos Stergiopoulos ; Laboratory of Inorganic and Analytical Chemistry, School of Chemical Engineering, National Technical University of Athens, Iroon Polytechniou 9, 157 80 Athens, Greece.
Anna Tsantili-Kakoulidou ; Laboratory of Pharmaceutical Chemistry, School of Pharmacy, University of Athens, Panepistimiopolis, Zografou, 157 71 Athens, Greece

Sažetak

Immobilized Artificial Membrane (IAM) chromatography constitutes a valuable tool for medicinal chemists to prioritize drug candidates in early drug development. The retention on IAM stationary phases encodes lipophilicity, electrostatic and other secondary interactions contrary to traditional octanol-water partitioning. An increasing number of publications in recent years have suggested that IAM indices, including isocratic log k(IAM) or extrapolated log kw(IAM) retention factors, chromatographic hydrophobicity index CHI(IAM) or the polarity parameter Δlog kw(IAM) can successfully model the passage of xeniobiotics through biological membranes and barriers and predict pharmacokinetic properties, often in combination with additional descriptors. Examples referring to the modeling of human oral absorption, blood-brain penetration and skin partition are described. More recently, IAM chromatography has been applied to estimate toxicological endpoints in regard to drug safety, such as phospholipidosis potential, or in regard to chemical risk hazards including the bioconcentration factor and aquatic organisms’ toxicity. The promising results in both medicinal chemistry and in environmental science in combination with the speed, reproducibility and low analyte consumption suggest that a broader application of IAM chromatography in the early drug discovery process and in ecotoxicity may save time and money in initial drug candidate selection and will contribute to a reduced risk hazard of chemicals.

Ključne riječi

IAM chromatography; lipophilicity; phospholipophilicity; membrane permeability; human oral absorption; ecotoxicity; aquatic toxicity; bioconcentration factor (BCF)

Hrčak ID:

205904

URI

https://hrcak.srce.hr/205904

Datum izdavanja:

22.9.2018.

Posjeta: 1.342 *