Probing biotransformation relationships among pyridoacridines by focusing on oxygenated analogues

Journal of Natural Products

Volumn 66, Issue 6, 2003, Pages 873-875

  Wenzel, Philip J ^a   Crews, Phillip ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 METHOXYAMPHIMIDINE; ACRIDINE DERIVATIVE; NEOAMPHIMIDINE; PYRIDOACRIDINE; UNCLASSIFIED DRUG;

AB INITIO CALCULATION; ARTICLE; BIOTRANSFORMATION; DRUG ISOLATION; OXYGENATION; POLARIZATION; SOLVATION; STRUCTURE ANALYSIS;

EID: 0038203575     PISSN: 01633864     EISSN: None     Source Type: Journal    
DOI: 10.1021/np020601z     Document Type: Article

References (18)

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4. See ref 3, Table S2.
5. By contrast the pentacyclic pyrroloacridines of the plakinidine family have been reported from both a sponge [(a) Inman, W. D.; O'Neill-Johnson, M.; Crews, P. J. Am. Chem. Soc. 1990, 112, 1-4. (b) West, R. R.; Mayne, C. L.; Ireland, C. M.; Brinen, L. S.; Clardy, J. Tetrahedron Lett. 1990, 31, 3271-3274] and a tunicate [(c) Ford, P.W.; Davidson, B. S. J. Nat. Prod. 1997, 60, 1051-1053. (d) Smith, C.J.; Venables, D. A.; Hopmann, C.; Salomon, C. E.; Jompa, J.; Tahir, A.; Faulkner, D. J.; Ireland, C. M. J. Nat. Prod. 1997, 60, 1048-1050].
6. By contrast the pentacyclic pyrroloacridines of the plakinidine family have been reported from both a sponge [(a) Inman, W. D.; O'Neill-Johnson, M.; Crews, P. J. Am. Chem. Soc. 1990, 112, 1-4. (b) West, R. R.; Mayne, C. L.; Ireland, C. M.; Brinen, L. S.; Clardy, J. Tetrahedron Lett. 1990, 31, 3271-3274] and a tunicate [(c) Ford, P.W.; Davidson, B. S. J. Nat. Prod. 1997, 60, 1051-1053. (d) Smith, C.J.; Venables, D. A.; Hopmann, C.; Salomon, C. E.; Jompa, J.; Tahir, A.; Faulkner, D. J.; Ireland, C. M. J. Nat. Prod. 1997, 60, 1048-1050].
7. By contrast the pentacyclic pyrroloacridines of the plakinidine family have been reported from both a sponge [(a) Inman, W. D.; O'Neill-Johnson, M.; Crews, P. J. Am. Chem. Soc. 1990, 112, 1-4. (b) West, R. R.; Mayne, C. L.; Ireland, C. M.; Brinen, L. S.; Clardy, J. Tetrahedron Lett. 1990, 31, 3271-3274] and a tunicate [(c) Ford, P.W.; Davidson, B. S. J. Nat. Prod. 1997, 60, 1051-1053. (d) Smith, C.J.; Venables, D. A.; Hopmann, C.; Salomon, C. E.; Jompa, J.; Tahir, A.; Faulkner, D. J.; Ireland, C. M. J. Nat. Prod. 1997, 60, 1048-1050].
8. By contrast the pentacyclic pyrroloacridines of the plakinidine family have been reported from both a sponge [(a) Inman, W. D.; O'Neill-Johnson, M.; Crews, P. J. Am. Chem. Soc. 1990, 112, 1-4. (b) West, R. R.; Mayne, C. L.; Ireland, C. M.; Brinen, L. S.; Clardy, J. Tetrahedron Lett. 1990, 31, 3271-3274] and a tunicate [(c) Ford, P.W.; Davidson, B. S. J. Nat. Prod. 1997, 60, 1051-1053. (d) Smith, C.J.; Venables, D. A.; Hopmann, C.; Salomon, C. E.; Jompa, J.; Tahir, A.; Faulkner, D. J.; Ireland, C. M. J. Nat. Prod. 1997, 60, 1048-1050].
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14. An alternative to the oxidation pathway proposed here is the action of a single enzyme. The "bay region" of polyaromatic hydrocarbons (PAH) such as benzo[a]pyrene undergoes epoxidization or hydroxylation by the action of a liver cytochrome p450. By analogy the bay region, position 5, of pyridoacridines may be subject to a similar cytochrome p450. See: (a) Stansbury, K. H., Flesher, J. W.; Gupta, R. C. Chem. Res. Toxicol. 1994, 7, 254-259. (b) Seidel, A.; Friedberg, T.; Lollmann, B.; Schwierzok, A.; Funk, M.; Frank, H.; Holler, R.; Oesch, F.; Glatt, H. Carcinogenesis 1998, 19, 1975-1981.
15. An alternative to the oxidation pathway proposed here is the action of a single enzyme. The "bay region" of polyaromatic hydrocarbons (PAH) such as benzo[a]pyrene undergoes epoxidization or hydroxylation by the action of a liver cytochrome p450. By analogy the bay region, position 5, of pyridoacridines may be subject to a similar cytochrome p450. See: (a) Stansbury, K. H., Flesher, J. W.; Gupta, R. C. Chem. Res. Toxicol. 1994, 7, 254-259. (b) Seidel, A.; Friedberg, T.; Lollmann, B.; Schwierzok, A.; Funk, M.; Frank, H.; Holler, R.; Oesch, F.; Glatt, H. Carcinogenesis 1998, 19, 1975-1981.
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