The interaction of cytosolic epoxide hydrolase with chiral epoxides |
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| Institution: | 1. Toxicogenomics Unit, National Institute of Public Health, Prague, Czech Republic;2. Centre for Systems Medicine, Department of Physiology, Royal College of Surgeons in Ireland, Dublin 2, Ireland;3. Biomedical Centre, Faculty of Medicine in Plzen, Charles University in Prague, Plzen, Czech Republic;1. Division of Animal Biotechnology, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST Kashmir, J&K, India;2. Department of Veterinary Clinical Medicine, Ethics and Jurisprudence, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST Kashmir, J&K, India;3. Division of Veterinary Biochemistry, Faculty of Veterinary Sciences & Animal Husbandry, SKUAST Kashmir, Jammu and Kashmir, India;4. ICL Group of Colleges, Kurukshetra University, Ambala, Haryana, India;5. Department of Biotechnology, Govt. Degree College, Anantnag, J&K, India;6. Division of Animal Biotechnology, Indian Veterinary Research Institute, Izatnagar, Uttar Pradesh, India;7. Department of Chemistry, Govt. Degree College Surankote, Poonch, J&K, India;8. Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia |
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| Abstract: | - 1.1. The kinetic parameters of the cytosolic epoxide hydrolase were examined with two sets of spectrophotometric substrates. The (2S,3S)- and (2R,3R)-enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-phenylpropyl carbonate had a Kmof 33 and 68 μm and a Vmax of 16 and 27 μmol/min/mg, respectively. With the (2S,3S)- and (2R,3R)- enantiomers of 4-nitrophenyl trans-2,3-epoxy-3-(4-nitrophenyl)propyl carbonate, cytosolic epoxide hydrolase had a KM of 8.0 and 15 μM and a Vmax of 7.8 and 5.0 μmol/min/mg, respectively.
- 2.2. Glycidyl 4-nitrobenzoate had the lowest I50 of the compounds tested in the glycidyl 4-nitrobenzoate series (I50= 140 μM). The I50 of the (2R)-enantiomer was 3.7-fold higher. The inhibitor with the lowest i50 in the glycidol series, and the lowest I50 of any compound tested, was (2S,3S)-3-(4-nitrophenyl)glycidol (I50 = 13.0μM). It also showed the greatest difference in I50 between the enantiomers (330-fold).
- 3.3. All enantiomers of glycidyl 4-nitrobenzoates and trans-3-phenylglycidols gave differential inhibition of cytosolic epoxide hydrolase. However, neither the (S,S)-/(S)- or (R,R)-/(R)-enantiomer always had the lower I50.
- 4.4. Addition of one or more methyl groups to either enantiomer of glycidyl 4-nitrobenzoate resulted in increased I50. However, addition of a methyl group to C2 of either enantiomer of 3-phenylglycidol resulted in a decreased I50. Finally, when the hydroxyl group of trans-3-(4-nitrophenyl)glycidol was esterified the I50 of the (2S,3S)- but not the (2R,3R)-enantiomer increased.
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