Structure-activity relationships of the ultrapotent vanilloid resiniferatoxin (RTX): The side chain benzylic methylene

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 1, 2010, Pages 97-99

  Appendino, Giovanni ^a   Ech Chahad, Abdellah ^a   Minassi, Alberto ^a   De Petrocellis, Luciano ^b   Marzo, Vincenzo Di ^b  

^a UNIVERSITY OF EASTERN PIEDMONT   (Italy)

^b CNR   (Italy)

Author keywords

Capsaicin; Resiniferatoxin (RTX); Structure activity relationships; TRPV1; Vanilloids

Indexed keywords

BENZYLIC METHYLENE; CARBENOID; RESINIFERATOXIN; UNCLASSIFIED DRUG;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CONTROLLED STUDY; DEPROTECTION REACTION; DIASTEREOISOMER; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; ESTERIFICATION; HUMAN; HUMAN CELL; METHYLATION; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION;

CELL LINE; DITERPENES; HUMANS; IODINE; METHYLATION; STRUCTURE-ACTIVITY RELATIONSHIP; TRPV CATION CHANNELS;

EID: 72149094339     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.11.035     Document Type: Article

References (19)

1. Isolation from Euphorbia resinifera Berg:. Hergenhahn M., Adolf W., and Hecker E. Tetrahedron Lett. 19 (1975) 1595
2. Isolation from E. poissonii Pax:. Schmidt R.J., and Evans F.J. J. Pharm. Pharmacol. 27 (1975) 50P
3. Szallasi A., and Blumberg P.M. Neuroscience 30 (1989) 515
4. Recent clinical studies: (a) Refractory detrusor overactivity: Kuo, H. C.; Liu, H. T.; Yang, W. C. J. Urol. 2006, 176, 641. (b) Cancer pain: Hartel, M.; di Mola, F. F.; Selvaggi, F.; Mascetta, G.; Wente, M. N.; Felix, K.; Giese, N. A.; Hinz, U.; De Sebastiano, P.; Buchler, M. W.; Friess, H. Gut 2006, 55, 519, and Ghilardi, J. R.; Robrich, H.; Lindsay, T. H.; Sevick, M. A.; Kubota, K.; Halvorson, K. G.; Poblete, J.; Chaplan, S. R.; Dubin, A. E.; Carruthers, N. I.; Swanson, D.; Kuskowski, M.; Flores, C. M.; Julius, D.; Manthyh, P. W. J. Neurosci. 2005, 25, 3126. RTX was found ineffective for the treatment of interstitial cystitis (Payne, C. K.; Mosbaugh, P. G.; Forrest, J. B.; Evans, R. J.; Withmore, K. E.; Antoci, J. P.; Perez-Marrero, R.; Jacoby, K.; Diokno, A. C.; O'Reilly, K. J.; Greibling, T. L.; Vasavada, S. P.; Yu, A. S.; Frumkin, L. R. J. Urol., 2005, 173, 1590).
5. Caterina M.J., Schumacher M.A., Tominaga M., Rosen T.A., Levine J.D., and Julius D. Nature 389 (1997) 816
6. Wahl P., Foged C., Tullin S., and Thomsen C. Mol. Pharmacol. 59 (2001) 9
7. Fattorusso E., Lanzotti V., Taglialatela-Scafati O., Tron G.C., and Appendino G. Eur. J. Org. Chem. (2002) 71
8. Walpole C.S.J., Bevan S., Bloomfield G., Breckenridge R., James I.F., Ritchie T., Szallasi A., Winter J., and Wrigglesworth R. J. Med. Chem. 39 (1996) 2939
9. Appendino G., Ech-Chahad A., Minassi A., Bacchiega S., De Petrocellis L., and Di Marzo V. Bioorg. Med. Chem. Lett. 17 (2007) 132
10. Choi H.K., Choi S., Lee Y., Kang D.W., Ryu H., Maeng H.J., Chung S.J., Pavlyukovets V.A., Pearce L.V., Toth A., Tran R., Wang Y., Morgan M.A., Blumberg P.M., and Lee J. Bioorg. Med. Chem. 19 (2009) 690
11. Vriens J., Appendino G., and Nilius B. Mol. Pharmacol. 75 (2009) 1262
12. Appendino G., Minassi A., Daddario N., Bianchi F., and Tron G.C. Org. Lett. 4 (2002) 3839
13. EM = 516 nm) before and after the addition of the test compounds at various concentrations. Kinetic effects (Szallasi, A.; Blumberg, P. M.; Annicelli, L. LK.; Krause, J. E.; Cortright, D. N. Mol. Pharmacol. 1999, 56, 581) were not observed in the calcium fluorescence assays as all compounds behaved exactly like RTX in terms of onset and duration of response.
14. Smith M.B., and March J. March's Advanced Organic Chemistry. 6th ed. (2007), Wiley, Hoboken, US
15. Appendino G., Cravotto G., Palmisano G., Annunziata R., and Szallasi A. J. Med. Chem. 39 (1996) 3123
16. +).
17. Appendino G., Daddario N., Minassi A., Schiano Morello A., De Petrocellis L., and Di Marzo V. J. Med. Chem. 48 (2005) 4663
18. Lu Y., Shi T., Wang Y., Yang H., Xiuhua Yan X., Xiaoming Luo X., Hualiang Jiang H., and Zhu W. J. Med. Chem. 52 (2009) 2854
19. Aakeröy C.B., Fasulo M., Schultheiss N., Desper J., and Moore C. J. Am. Chem. Soc. 129 (2007) 13772