Cytochrome selectivity

Onderwater, R. C., Venhorst, J., Commandeur, J. N., and Vermeulen, N. P. (1999) Design, synthesis, and characterization of 7-methoxy-4-(aminomethyl)coumarin as a novel and selective cytochrome P450 2D6 substrate suitable for high-throughput screening. Chem. Res. Toxicol. 12, 555-559. 

Halpert, J. R. (1995) Structural basis of selective cytochrome P450 inhibition. Annu. Rev. Pharmacol. Toxicol. 35, 29-53. 

Zenk, M.H., Gerardy, R. and Stadler, R. (1995) Phenol oxidative coupling of ben-zylisoquinoline alkaloids is catalyzed by regio- and stereo-selective cytochrome P450 linked plant enzymes salutaridine and berbamrmine.. Chem. Soc. Chem. Com-mun., pp. 1725-27. 

TABLE 15.1 Selected Cytochrome P450 Substrates/ Inhibitors/ and Inducers... 

Kwon, H., Sahali, Y, Skipper, P. L., and Xannenbaum, S. R. (1992). Oxidation of cyclopenta[cmouse liver microsomes and selected cytochrome P450 enzymes. Chem Res Toxicol 5,... 

Ren S, Zeng J, Mei Y, Zhang JZ, Yan SF, Fei J, Chen L (2013) Discovery and characterization of novel, potent, selective cytochrome P450 2J2 inhibitors. Drug Metab Dispos 41 60-71... 

Korhonen LE, Turpeinen M, Rahnasto M, Witte-kindt C, Poso A, Pelkonen O, Raunio H, Juvonen RO (2007) New potent and selective cytochrome P450 2B6 (CYP2B6) inhibitors based on three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis. Br J Pharmacol 150 932-942... 

Kartha JS, Yost GS (2008) Mechanism-based inactivation of lung-selective cytochrome P450 CYP2F enzymes. Drug Metab Dispos 36 155-162... 

Parys, S., Kehraus, S., Krick, A., Glombitza, K.-W., Carmeli, S., Klimo, K., Gerhauser, C., and Kdtrig, G.-M. (2010) In vitro chemopreventive potential of fiicophlorethols from the brown alga Fucus vesiculosus L by anti-oxidant activity and inhibition of selected cytochrome P450 enzymes. Phytodiemistry, 71, 221-229. 

In addition to halopeiidol, the putative neuroleptics, limcazole (311), lemoxipiide (312), and gevotioline (313) bind to (7-ieceptois as does the dopamine uptake blocker, GBR 12909 (314) and two ligands active at the NMDA receptor, ifenprodil (315) and CNS 1102 (316). NPC 16377, (317) is a selective (7-teceptor ligand. MAO inhibitors and antidepressants also bind to (7-teceptors. Some evidence indicates that (7-teceptors in the brain are in fact a form of cytochrome which may account for the diversity of ligands interacting with (7-sites. 

Atovaquone, a hydroxynaphthoquinone, selectively inhibits the respiratory chain of protozoan mitochondria at the cytochrome bcl complex (complex III) by mimicking the natural substrate, ubiquinone. Inhibition of cytochrome bcl disrupts the mitochondrial electron transfer chain and leads to a breakdown of the mitochondrial membrane potential. Atovaquone is effective against all parasite stages in humans, including the liver stages. 

The other major mechanism of pyrethroid resistance found in some field strains of Heliothis virescens was enhanced detoxication due to a high rate of oxidative detoxication, mediated by a form of cytochrome P450 (McCaffery 1998). Some strains, such as PEG 87, which was subjected to a high level of field and laboratory selection, possessed both mechanisms. Other example of pyrethroid resistance due to enhanced detoxication may be found in the literature on pesticides. 

Ma, R., Cohen, M.B., and Berenbaum, M.R. et al. (1994). Black swallowtail alleles encode cytochrome P450s that selectively metabolise linear furanocoumarins. Archives of Biochemistry and Biophysics 310, 332-340. 

In some cases, small biological redox partner proteins such as heme-containing cytochromes, ferredoxins comprising an iron-sulfur cluster, or azurin with a mononuclear Cu site have been used as natural mediators to facilitate fast electron exchange with enzymes. A specific surface site on the redox protein often complements a region on the enzyme surface, and enables selective docking with a short electron tunneling... 

Lanza, D. L. Yost, G. S. Selective dehydrogenation/oxygenation of 3-methylindole by cytochrome P450 enzymes. Drug Metab. Dispos. 2001, 29, 950-953. 

---