Synthesis and bioevaluation of hybrid 4-aminoquinoline triazines as a new class of antimalarial agents

Bioorganic and Medicinal Chemistry Letters

Volumn 18, Issue 24, 2008, Pages 6530-6533

  Kumar, Ashok ^a   Srivastava, Kumkum ^a   Raja Kumar, S ^a   Puri, S K ^a   Chauhan, Prem M S ^a  

^a CENTRAL DRUG RESEARCH INSTITUTE   (India)

Author keywords

4 Aminoquinoline; Antimalarial; P. falciparum; Triazine

Indexed keywords

4 AMINOQUINOLINE DERIVATIVE; 4 AMINOQUINOLINE TRIAZINE DERIVATIVE; ANTIMALARIAL AGENT; CHLOROQUINE; TRIAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG SYNTHESIS; IC 50; MALARIA; MOUSE; NONHUMAN; PLASMODIUM FALCIPARUM; PLASMODIUM YOELII; REACTION ANALYSIS; VERO CELL;

AMINOQUINOLINES; ANIMALS; ANTIMALARIALS; CHEMISTRY, PHARMACEUTICAL; CHLOROGUANIDE; CHLOROQUINE; DRUG DESIGN; ERYTHROCYTES; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, CHEMICAL; PARASITIC SENSITIVITY TESTS; PLASMODIUM FALCIPARUM; PLASMODIUM YOELII; TRIAZINES;

PLASMODIUM FALCIPARUM;

EID: 56249130079     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2008.10.049     Document Type: Article

References (29)

1. Ursos L.M.B., and Roepe P.D. Med. Res. Rev. 22 (2002) 465
2. Kumar A., Latoya S.B., Agarwal A., and Chauhan P.M.S. Curr. Med. Chem. 10 (2003) 1137
3. Kumar A., Katiyar S.B., Agarwal A., and Chauhan P.M.S. Drug Future 28 (2003) 243
4. Frevert U. Trends Parasitol. 20 (2004) 417
5. Ridley R.G. Nature 415 (2002) 686
6. White N.J. Lancet 353 (1999) 65
7. Friebolin W., Jannack B., Wenzel N., Furrer J., Oeser T., Sanchez C.P., Lanzer M., Yardley V., Becker K., and Davioud- charvet E. J. Med. Chem. 51 (2008) 1260
8. Egan T.J. Drug Des. Rev. 1 (2004) 93
9. Fidock D.A., Nomura T., Talley A.K., Cooper R.A., Dzekunov S.M., Ferdig M.T., Ursos L.M., Sidhu A.B., Naude B., Deitsch K.W., Su X.Z., Wootton J.C., Roepe P.D., and Wellems T.E. Mol. Cell 6 (2000) 861
10. Wellems T.E. Science 298 (2002) 124
11. Vippagunta S.R., Dorn A., Matile H., Bhattacharjee A.K., Karle J.M., Ellis W.Y., Ridely R.G., and Vennerstrom J.L. J. Med. Chem. 42 (1999) 4630
12. Egan T.J., Hunter R., Kaschula C.H., Marques H.M., Misplon A., and Walden J. J. Med. Chem. 43 (2000) 283
13. Srinivas R., Maiti C.S., Dorn A., Scorneaux B., Bhattacharjee A.K., and Ellis W.Y. J. Med. Chem. 46 (2003) 3166
14. Chiyanzu I., Clarkson C., Smith P.J., Lehman J., Gut J., Rosenthal P.J., and Chibale K. Bioorg. Med. Chem. 13 (2005) 3249
15. Gupta L., Srivastava K., Singh S., Puri S.K., and Chauhan P.M.S. Bioorg. Med. Chem. Lett. 18 (2008) 3306
16. Singh C., Malik H., and Puri S.K. Bioorg. Med. Chem. 12 (2004) 1177
17. Dechy-Cabaret O., Benoit-Vical F., Robert A., and Meunier B. ChemBioChem 1 (2000) 281
18. Beagley P., Blackie M.A.L., Chibale K., Clarkson C., Meijboom R., Moss J.R., Smith P.J., and Su H. Dalton Trans. 15 (2003) 3046
19. Flipo M., Florent I., Grellier P., Sergheraert C., and Deprez-Poulain R. Bioorg. Med. Chem. Lett. 13 (2003) 2659
20. Burgess S.J., Selzer A., Kelly J.X., Smilkstein M.J., Riscoe M.K., and Peyton D.H. J. Med. Chem. 49 (2006) 5623
21. Blakley R.L. Dihydrofolate Reductase. In: Blakley R.L., and Benkovic S.J. (Eds). Folates and Pteridines Vol. 1 (1984), Wiley, New York 191-253
22. Agarwal A., Srivastava K., Puri S.K., and Chauhan P.M.S. Bioorg. Med. Chem. Lett. 15 (2005) 531
23. Katiyar S.B., Srivastava K., Puri S.K., and Chauhan P.M.S. Bioorg. Med. Chem. Lett. 15 (2005) 4957
24. De D., Krogstad F.M., Byers L.D., and Krogstad D.J. J. Med. Chem. 41 (1988) 4918
25. Lundt L., and Madsen R. Synthesis (1992) 1129
26. 50) was determined using non-linear regression analysis dose-response curves. Smilkstein, M.; Sriwilaijaroen, N.; Kelly, J. X.; Wilairat, P.; Riscoe, M. Antimicrob. agents Chemother. 2004, 48, 1803-1806.
27. 50) was determined using non-linear regression analysis dose-response curves and represented the concentration of compound required to kill 50% of the fibroblast cells. Mosmann T. J. Immunol. Methods. 1983, 65, 55.
28. The in vivo drug response was evaluated in Swiss mice infected with P. yoelii (N-67 strain) which is innately resistant to CQ. The mice (22 ± 2 g) were inoculated with 1 × 1 parasitized RBC on day 0 and treatment was administered to a group of five mice from day 0 to 3, once daily. The aqueous suspensions of compounds were prepared with a few drops of Tween 80. The efficacy of test compounds was evaluated at 50 mg/kg/day and required daily dose was administered in 0.2 mL volume via intraperitoneal route. Parasitaemia levels were recorded from thin blood smears between days 4 and 6. The mean value determined for a group of five mice was used to calculate the percent suppression of parasitaemia with respect to the untreated control group. Mice treated with CQ served as reference controls. Puri, S. K.; Singh, N. Exp. Parasitol. 2000, 94, 8.
29. 9: Calcd C 63.31, H 7.33, N 22.91. Found: C 63.42, H 7.21, N 22.79.