The biomimetic iron-mediated degradation of arteflene (Ro-42-1611), an endoperoxide antimalarial: Implications for the mechanism of antimalarial activity

Tetrahedron Letters

Volumn 38, Issue 24, 1997, Pages 4263-4266

  O' Neill, Paul M ^a   Bishop, Laurence P ^a   Searle, Natalie L ^a   Maggs, James L ^a   Ward, Stephen A ^a   Bray, Patrick G ^a   Storr, Richard C ^a   Park, B Kevin ^a  

^a UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARTEFLENE; FERROUS ION; HEMIN; RADICAL;

ANTIMALARIAL ACTIVITY; ARTICLE; DRUG DEGRADATION; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY;

EID: 0030976258     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00874-5     Document Type: Article

References (15)

1. Jefford, C.W.; Kohmoto, S.; Jaggi, D.; Timari, J.; Rossier, J.C.; Rudaz, M.; Barbuzzi, O.; Gerard, D.; Burger, U.; Kamalaprija, P.; Mareda, J.; Bernardinelli, G.; Manzanares, I.; Canfield, C.J.; Fleck, S.L.; Robinson, B.L.; Peters, W. Helv. Chim. Acta., 1995, 78, 647
2. Hofheinz, W.; Burgin, H.; Gocke, E.; Jaquet, R.; Masciadri, R.; Schmid, S.; Stohler, H.; Urwyler, H. Trop. Med. Parasitol, 1994, 45, 261
3. Meshnick, S.R.; Jefford, C.W.; Posner, G.H.; Avery, M.A. Parasitol Today, 1996, 12, 79
4. Hong, Y.; Zang, Y.; Meshnick, S.R., Mol. Biochem. Parasitol., 1994, 63, 121
5. For a detailed investigation of iron (II) catalysed decomposition of an oxygen-18-labeled 1,2,4-trioxane see: Posner, G.H.; Oh, C.H., J. Am. Chem. Soc., 1992, 114, 8328
6. For an excellent study that implicates the intermediacy of an Fe(IV)=O see: Posner, G.H.; Cumming, J.N.; Ploypradith, P.; Oh, C.H., J. Am. Chem. Soc., 1995, 117, 5885-5886
7. Haynes, R.K.; Vonwiller, S.C. Tetrahedron Lett., 1996, 37, 257-260
8. Posner, G.H.; Oh, C.H.; Wang, D.; Gerena, L.; Milhous, W.K.; Asamahasadka, W. J. Med. Chem., 1994, 37, 1256
9. Jefford., C.W.; Vicente, M.G.H.; Jacquier, Y.; Favarger, F.; Mareda, J.; Millasson-Schmidt, P.; Brunner, G.; Burger, U., Helv. Chim. Acta., 1996, 79, 1475-1487
10. 4O, 52); CIMS 565 (2M + 1, 56), 283(M+1, 100), 263 (M+1-HF, 80). Anal. Required C, 51.08 H, 2.86, Found C, 51.5, H, 2.98
11. Jefford, C. W.; Favarger, F.; da Graca, M.; Vicente, H.; Jacquier, Y. Helv. Chim. Acta, 1995, 78, 452-458
12. Haynes, R.K.; Vonwiller, S.C.; Tetrahedron Lett., 1996, 37, 253-256
13. Attempts at trapping the cyclohexyl fragment failed. In addition no adduct of heme and arteflene was observed in the reactions involving heroin.
14. Desjardins, R.E.; Canfield, J ; Haynes, D.; Chulay, D.J. , Quantitative , Antimicrob. Agents. Chemother., 1979, 16, 710-718.
15. In studies conducted with radiolabelled arteflene it was noted by Meshnick et al. (Antimicrob. Agents. Chemother., 1994, 38, 1854-1858) that several specific malarial proteins were alkylated by arteflene. Since the radio-label is in the vinyl function of arteflene it seems reasonable that the protein-arteflene adducts described in this study are in fact derived from reaction of the enone 6 with protein thiol groups.