Phase 2 enzyme inducers

Dinkova-Kostova AT, Abeygunawardana C, Talalay P. 1998. Chemoprotective properties of phenylpropenoids, bis(benzylidene)cycloalkanones, and related Michael reaction acceptors Correlation of potencies as phase 2 enzyme inducers and radical scavengers. J Med Chem 41 5287-5296. 

Wettasinghe, M. et al.. Phase II enzyme-inducing and antioxidant activities of beetroot Beta vulgaris L.) extracts from phenotypes of different pigmentation, J. Agric. Food Chem., 50, 6704, 2002. 

Cottrell, S., Oliver, K., Lake, B.G. Powell, C.J. (1996) Strain-specific enhancement or inhibition of coumarin hepatotoxicity in mice following pretreatment with two different liver enzyme-inducing agents. Fundam. appl. Toxicol, 34, 47-55 Cox, D., O Kennedy, R. Thornes, R.D. (1989) The rarity of liver toxicity inpatients treated with coumarin (1,2-benzopyrone). Hum. exp. Toxicol, 8, 501-506 Dexeus, E.H., Logothetis, C.J., Sella, A., Fitz, K., Amato, R., Reuben, J.M. Dozier, N. (1990) Phase II study of coumarin and cimetidine in patients with metastatic renal cell carcinoma. J. din. Oncol, 8, 325-329... 

The a, p-unsaturated diketone moiety in the curcuminoids is a Michael reaction acceptor, which belongs to the major class of phase II enzyme inducers... 

Subcellular localization studies have identified P-450-dependent monooxygenase activity in adult hairless mice sebaceous glands. Phase II conjugation pathways have also been identified in skin. Extracellular enzymes including esterases are present in skin, which has been utilized to formulate lipid-soluble ester prodrugs which penetrate the stratum corneum and then are cleaved to release active drug into the systemic circulation. Finally, co-administration of enzyme inducers and inhibitors modulate cutaneous biotransformation and thus alter the systemic toxicity profile. These metabolic interactions that occur in skin have attracted a great deal of research attention and clearly illustrate that skin is more than a passive barrier to toxin absorption. 

In summary, gossypol is believed to arrest cell growth at the Go/Gi phase and induce cell apoptosis, in cancer cells, by regulating the cell cycle, enzymes, antiapoptosis, and proapoptosis proteins. 

The dependence of enantioselectivity in microbial transformations on the cultivation conditions of the microorganisms has also been investigated182-861. The enzymes induced during the growth phase and during starvation are certainly different, therefore the enantioselectivity of the product may be different when two competing enzymes with different enantioselectivities catalyze the reduction. Since the enzyme... 

In order to search for new chemopreventive enzyme inducers and to elucidate the structural features responsible for the ability of curcumin to induce Phase 2 detoxification enzymes, Dinkova-Kostova et al.[48, 49] examined some natural as well as synthetic curcumin analogs for ability to induce NAD(P)H quinone reductase (a prototype for phase 2 detoxification enzymes) in murine hepatoma cells. Compounds... 

Carbamazepine is metabolized primarily by oxidation by the CYP 3A4 isozyme of hepatic cytochrome P45f). The primary metabolite is a pharmacologically active 10,10 epoxide, which undergoes phase II glucuronidation. Carbamazepine is a potent enzyme inducer, and increases its own rate of metabolism throughout the induction of cytochrome P45f). 

Unfolding of protein ions in the gas phase was induced by collision activation with argon, and the cross section of unfolded conformation was measured and compared with that of the more compact and stable folded conformation. In another publication, TW-IMS-MS was used to measure cross sections to show that a protein retained its solution conformation of both recombinant and solvent-disrupted versions. TW-IMS-MS was also used to study the speciation of different ions bound to bovine carbonic anhydrase, and the conclusion was that ions that are strongly bound to the enzyme (Zn and Cu+ ) modify its structure more than weakly bound ions. ... 

Aucubin (15) isolated from the leaves of Aucuba japonica exhibited cytotoxic effect against cancer A-549 cells by blocking the cell cycle progression in the G(0)/G( 1) phase and inducing apoptosis. An enzyme-linked immunosorbent assay (ELISA) showed that the G(0)/G(1) phase arrest was possibly due to p53-mediated induction of p21 [143]. 

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