Effect of Binding Linkers on the Efficiency and Metabolite Profile of Biomimetic Reactions Catalyzed by Immobilized Metalloporphyrin.
György T BaloghBalázs DecsiRéka KrammerBalázs KenézFerenc EnderTamás HergertLászló PoppePublished in: Metabolites (2022)
The investigation of liver-related metabolic stability of a drug candidate is a widely used key strategy in early-stage drug discovery. Metalloporphyrin-based biomimetic catalysts are good and well-described models of the function of CyP450 in hepatocytes. In this research, the immobilization of an iron porphyrin was performed on nanoporous silica particles via ionic interactions. The effect of the metalloporphyrin binding linkers was investigated on the catalytic efficiency and the metabolic profile of chloroquine as a model drug. The length of the amino-substituted linkers affects the chloroquine conversion as well as the ratio of human major and minor metabolites. While testing the immobilized catalysts in the continuous-flow reactor, results showed that the presented biomimetic system could be a promising alternative for the early-stage investigation of drug metabolites regarding analytical or synthetic goals as well.
Keyphrases
- early stage
- drug discovery
- metal organic framework
- ms ms
- endothelial cells
- ionic liquid
- drug induced
- highly efficient
- liver injury
- magnetic nanoparticles
- photodynamic therapy
- molecular docking
- tissue engineering
- emergency department
- dna binding
- public health
- rectal cancer
- radiation therapy
- transcription factor
- mass spectrometry
- anaerobic digestion
- capillary electrophoresis
- quantum dots
- neoadjuvant chemotherapy
- global health
- high speed