New functionalized 1,2,4-trioxepanes: Synthesis and antimalarial activity against multi-drug resistant P. yoelii in mice

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 19, 2008, Pages 5190-5193

  Singh, Chandan ^a   Pandey, Shilpi ^a   Kushwaha, Ambuj K ^a   Puri, Sunil K ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

1,2,4 Trioxane; 1,2,4 Trioxepane; Amino functionalized trioxepane; Antimalarial; Artemisinin; Ester functionalized trioxepane

Indexed keywords

OXEPANE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CLEARANCE; DRUG SCREENING; DRUG SYNTHESIS; MOUSE; MULTIDRUG RESISTANCE; NONHUMAN; PARASITEMIA; PLASMODIUM YOELII; TREATMENT RESPONSE;

ADMINISTRATION, ORAL; ANIMALS; ANTIMALARIALS; ARTEMISININS; COMBINATORIAL CHEMISTRY TECHNIQUES; DRUG RESISTANCE, MULTIPLE; HETEROCYCLIC COMPOUNDS; MICE; PARASITEMIA; PLASMODIUM YOELII; PROPANOLS; STRUCTURE-ACTIVITY RELATIONSHIP;

MUS; PLASMODIUM YOELII;

EID: 52049096404     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.08.096     Document Type: Article

References (58)

1. Klayman D.L. Science 228 (1985) 1049
2. Luo X.D., and Shen C.C. Med. Res. Rev. 7 (1987) 29
3. Zaman S.S., and Sharma R.P. Heterocycles 32 (1991) 1593
4. Zhou W.S., and Xu X.X. Acc. Chem. Res. 27 (1994) 211
5. Bhattacharya A.K., and Sharma R.P. Heterocycles 51 (1999) 1681
6. Borstnik K., Paik I., Shapiro T.A., and Posner G.H. Int. J. Parasitol. 32 (2002) 1661
7. Ploypradith P. Acta Trop. 89 (2004) 329
8. O'Neill P.M., and Posner G.H. J. Med. Chem. 47 (2004) 2945
9. Posner G.H., Chang W., Hess L., Woodard L., Sinishtaj S., Usera A.R., Maio W., Rosenthal A.S., Kalinda A.S., Angelo J.G.D., Peterson K.S., Stohler R., Chollet J., Santo Tomas J., Synder C., Rottmann M., Wittlin S., Brun R., and Shapiro A.T. J. Med. Chem. 51 (2008) 1035
10. Jefford C.W., Jaggi D., Boukouvalas J., and Kohmoto S. J. Am. Chem. Soc. 105 (1983) 6498
11. Kepler J.A., Philip A., Lee Y.W., Morey M.C., and Caroll F.I. J. Med. Chem. 31 (1988) 713
12. Fujisakum T., Miura M., Nojima M., and Kasabayashi S. J. Chem. Soc., Perkin Trans. 1 (1989) 1031
13. Avery M.A., Jennings-White C., and Chong W.K.M. J. Org. Chem. 54 (1989) 1792
14. Singh C. Tetrahedron Lett. 31 (1990) 6901
15. Bloodworth A.J., and Shah A. J. Chem. Soc. Chem. Commun. (1991) 947
16. Posner G.H., Oh C.H., and Milhous W.K. Tetrahedron Lett. 32 (1991) 4235
17. Bunnelle W.H., Isbell T.A., Barnes C.L., and Qualls S. J. Am. Chem. Soc. 113 (1991) 8168
18. Singh C., Misra D., Saxena G., and Chandra S. Bioorg. Med. Chem. Lett. 2 (1992) 497
19. Bloodworth A.J., and Johnson K.A. Tetrahedron Lett. 35 (1994) 8057
20. Singh C., Misra D., Saxena G., and Chandra S. Bioorg. Med. Chem. Lett. 5 (1995) 1913
21. O'Neill P.M., Pugh M., Davies J., Ward S.A., and Park B.K. Tetrahedron Lett. 42 (2001) 4569
22. Singh C., Gupta N., and Puri S.K. Bioorg. Med. Chem. Lett. 12 (2002) 1913
23. Dechy-Carbet O., Robert A., and Meunier B. C.R. Chimie 5 (2002) 297
24. Dechy-Cabart O., Benoit-Vical F., Robert A., Magnaval J.-F., Seguda J.-P., and Meunier B. C.R. Chimie 6 (2003) 153
25. Singh C., Srivastav N.C., and Puri S.K. Bioorg. Med. Chem. 12 (2004) 5745
26. Singh C., Gupta N., and Puri S.K. Bioorg. Med. Chem. 12 (2004) 5553
27. O'Neill P.M., Mukhtar A., Ward S.A., Bickley J.F., Davies J., Bachi M.D., and Stocks P.A. Org. Lett. 6 (2004) 3035
28. Singh C., Malik H., and Puri S.K. J. Med. Chem. 49 (2006) 2794
29. Singh C., Kanchan R., Sharma U., and Puri S.K. J. Med. Chem. 50 (2007) 521
30. Singh C., Sharma U., Saxena G., and Puri S.K. Bioorg. Med. Chem. Lett. 17 (2007) 4097
31. Adam W., and Duran N. J. Chem. Soc. Chem. Commun. (1972) 798
32. Dussault P.H., and Davies D.R. Tetrahedron Lett. 37 (1996) 463
33. Ushigoe Y., Kano Y., and Nojima M. J. Chem. Soc., Perkin Trans. 1 (1997) 5
34. Ushigoe Y., Torao Y., Masuyama A., and Nojima M. J. Org. Chem. 62 (1997) 4949
35. Ushigoe Y., Masuyama A., Nojima M., and McCullough K.J. Tetrahedron Lett. 38 (1997) 8753
36. Oh C.H., and Kang J.H. Tetrahedron Lett. 39 (1998) 2771
37. Dussault P.H., Trullinger T.K., and Noor-e-Ain F. Org. Lett. 4 (2002) 4591
38. Ahmed A., and Dussault P.H. Org. Lett. 6 (2004) 3609
39. Amewu R., Stachulski A.V., Berry N.G., Ward S.A., Davies J., Labat G., Rossignol J.F., and O'Neill P.M. Bioorg. Med. Chem. Lett. 16 (2006) 6124
40. Singh C., Pandey S., Saxena G., Srivastava N., and Sharma M. J. Org. Chem. 71 (2006) 9057
41. Singh C., Pandey S., Sharma M., and Puri S.K. Bioorg. Med. Chem 16 (2008) 1816
42. Todorovic N.M., Stefanovic M., Tinant B., Declercq J.P., Makler M.T., and Solaja B.A. Steroids 61 (1996) 688
43. Opsenica D., Pocsfalvi G., Juranic Z., Tinant B., Declercq J.P., Kyle P.E., Milhous W.K., and Solaja B.A. J. Med. Chem. 43 (2000) 3274
44. Solaja B.A., Terzic N., Pocsfalvi G., Gerena L., Tinant B., Opsenica D., and Milhous W.K. J. Med. Chem. 45 (2002) 3331
45. Opsenica D., Angelovski G., Pocsfalvi G., Juranic Z., Zizak Z., Kyle D., Milhous W.K., and Solaja B.A. Bioorg. Med. Chem. 11 (2003) 2761
46. Opsenica I., Terzik N., Opsenica D., Angelovsky G., Lehnig M., Eilbracht P., Tinant B., Zizak Z., Smith K.S., Yang Y.S., Diaz D.S., Smith P.L., Milhous W.K., Dokovic D., and Solaja B.A. J. Med. Chem. 49 (2006) 3790
47. Ellis G.L., Ameu R., Sabbani S., Stocks P.A., Shone A., Stanford D., Gibbons P., Davies J., Vivas L., Charnaud S., Bongard E., Hall C., Rimmer K., Lozanom S., Jesus M., Gargallo D., Ward S.A., and O'Neill P.M. J. Med. Chem. 51 (2008) 2170
48. Vennerstrom J.L., Arbe-Barnes S., Brun R., Charman S.A., Chiu F.C.K., Chollet J., Dong Y., Dorn A., Hunziker D., Matile H., Mclntosh K., Padmanilayam M., Tomas J.S., Scheurer C., Scorneaux B., Tang Y., Urwyler H., Wittlin S., and Charman W.N. Nature 430 (2004) 900
49. Dong Y., Chollet J., Matile H., Charman S.A., Chiu F.C.K., Charman W.N., Scorneaux B., Urwyler H., Santo Tomas J., Scheurer C., Synder C., Dorn A., Wang X., Karle J.M., Tang Y., Wittlin S., Brun R., and Vennerstrom J.L. J. Med. Chem. 48 (2005) 4953
50. Dong Y., Tang Y., Chollet J., Matile H., Wittlin S., Charman S.A., Charman W.N., Santo Tomas J., Scheurer C., Synder C., Scorneaux B., Wang X., Padmanilayam M., Cheruku S.R., Brun R., and Vennerstrom J.L. Bioorg. Med. Chem. 14 (2006) 6368
51. Padmanilayam M., Scorneaux B., Dong Y., Chollet J., Matile H., Charman S.A., Creek D.J., Charman W.N., Santo Tomas J., Scheurer C., Wittlin S., Brun R., and Vennerstrom J.L. Bioorg. Med. Chem. Lett. 14 (2006) 5542
52. Tang Y., Dong Y., Wittlin S., Charman S.A., Chollet J., Chiu F.C.K., Charman W.N., Matile H., Urwyler H., Dorn A., Bajpai S., Wang X., Padmanilayam M., Kaele J.M., Brun R., and Vennerstrom J.L. Bioorg. Med. Chem. Lett. 17 (2007) 1260
53. Zhou L., Alker A., Ruf A., Wang X., Chiu F.C.K., Morizzi J., Charman S.A., Charman W.N., Scheurer C., Wittlin S., Dong Y., Hunziker D., and Vennerstrom J.L. Bioorg. Med. Chem. Lett. 18 (2008) 1555
54. The corresponding dispiro-bis-1,2,4-trioxepanes are formed as minor products; data not included.
55. 3: 509.2178. Found: 509.2171.
56. -1) 1721.
57. 6 parasitized RBC on day zero and treatment was administered to a group of five mice at each dose, from days 0 to 3, in two divided doses daily. The drug dilutions were prepared in groundnut oil so as to contain the required amount of the drug (1.2 mg for a dose of 96 mg/kg,) in 0.1 mL and administered either orally or intramuscularly for each dose. Parasitaemia level were recorded from thin blood smears between day 4 and 28. Mice treated with β-arteether served as positive controls.
58. 100% suppression of parasitaemia means no parasites were detected in 50 oil immersion microscopic fields (parasites if at all present are below the detection limit). The parasites present below the detection limit can multiply and eventually can be detected during observation on subsequent days. In such cases though the drug is providing near 100% suppression of the parasitaemia on day 4 but will not provide full protection to the treated mice in the 28 days survival assay.