1, 5 - bis (4 - methoxyphenyls) - 6, 7 - Dioxa-bicyclo [3.2.2] nonane's Anti-toxoplasmosis Effect that was Separated in Artemisin annula

개똥쑥에서 분리 확인된 endoperoxide ring 구조를 갖는 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane의 항톡소포자충 효과

  • Jiang, Jing-Hua (Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine) ;
  • Kim, Hwa-Kyoung (Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine) ;
  • Kim, Hye-Sook (Faculty of Pharmaceuticalsciences, Okayama University) ;
  • Kamata, Masaki (Faculty of Education and Human Sciences Mathematical and Natural Sciences, Niigata University) ;
  • Wataya, Yusuke (Faculty of Pharmaceuticalsciences, Okayama University) ;
  • Park, Hyun (Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine)
  • 강경화 (원광대학교 의과대학 인수공통감염병연구센터 및 감염생물학교실) ;
  • 김화경 (원광대학교 의과대학 인수공통감염병연구센터 및 감염생물학교실) ;
  • 김혜숙 (오카야마대학교 약학대학 의약품정보학교실) ;
  • 카마타 (니이가타대학교 교육인간 과학대학 자연정보강좌) ;
  • 와타야 (오카야마대학교 약학대학 의약품정보학교실) ;
  • 박현 (원광대학교 의과대학 인수공통감염병연구센터 및 감염생물학교실)
  • Published : 2007.02.25

Abstract

The Chinese medicinal plant Artemisia annua is the source of the antimalarial compound artemisinin. By the way, Artemisin annula was known have endoperoxide ring structure is included and has anti-malarial effect. Malaria and Toxoplasma gondii (T. gondii) is belong to Apicomplexa genera. So, confirmed whether we go compound 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane that have endoperoxide ring structure and there is anti-toxoplasmosis effect. The efficacy of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2] nonane alone was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were peformed with HeLa cell cultures, with quantification of Toxoplasma growth by a cell proliferation assay. Selectivity of 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane was 4.9 in vitro cell proliferation assay, this is higher than sulfadiazine (selectivity was 1.63). For in vivo studies, mice were acutely infected intraperitoneally with 10$^5$ tachyzoites of the virulent RH strain and then treated perorally for 4 days from 6 hours postinfection. Efficacy was assessed by sequential determination of parasite burdens in peritoneal cavity. in vitro, 1,5-bis(4-methoxyphenyl)-6,7-dioxa-bicyclo[3.2.2]nonane inhibited Toxoplasma growth at a concentration of 150mg/kg of body weight per day, the inhibition ratio was estimated to be 85.72%.

Keywords

References

  1. Hoffman, S.L., Subramanian, G.M., Collins, F.H., Venter, C. Plasmodium, human and Anopheles genomics and malaria, Nature, 415(6872):702-709, 2000 https://doi.org/10.1038/415702a
  2. Xu, P., Widmer, G., Wang, Y.P., Oazki, L.S., Alves, J.M., Serrano, M.G., Pulu, D., Manque, P., Akiyoshi, D., Mackey, A.J., Pearson, W.R., Dear, P.H., bankier, A.T., Peterson, D.L., Abrahamsen, M.S., Kapur, V., Tzipirl, S., Buck, G.A. The genome of Cryptosporidium hominis, Nature, 431(7012):1107-1112, 2004 https://doi.org/10.1038/nature02977
  3. Nicolle, M.M.C., Manceaux, L. Sun un protozoaire nouveau du gondi(Toxoplasma n. sp.), Arch Inst Pastrur Tunis. 2: 97, 1909
  4. Hutchison W.M., Dunachie, J.F., Siim, J.C., Work, K. Life cycle of Toxoplasma gondii, Br Med J., 4(5686): 806, 1969
  5. Dubey, J.P., Miller, N.L., Frenke, J.K. Toxoplasma gondii life cycle in cats, J Am Vet Med Assoc. 157(11):1767-1770, 1970
  6. Tenter, A.T., Heckeroth, A.R., Weiss, L.M. Toxoplasma gondii: from animals to humans, Int J Parasitol. 30(12-13): 1217-1258, 2000 https://doi.org/10.1016/S0020-7519(00)00124-7
  7. Montoya, J.G., Liesenfeld, L. Toxoplasmosis, Lancet, 363(12):1965-1976, 2004 https://doi.org/10.1016/S0140-6736(04)16412-X
  8. Luft, B.J., Remington, J.S. Toxoplasmic encephalitis in AIDS, Clin Infect Dis. 15(2):211-222, 1992 https://doi.org/10.1093/clinids/15.2.211
  9. Abdin, M.Z., Israr, M., Rehman, R.U., Jain, S.K. Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production, Plasta Med. 69(4):289-299, 2003 https://doi.org/10.1055/s-2003-38871
  10. Li, Y., Wu, Y.L. How Chinese scientists discovered qinghaosu (artemisinin) and developed its derivatives? What are the future perspectives?, Med Trop. 58(3):9-12, 1998
  11. Song, H.O., Ahn, M.H., Ryu, J.S., Min, D.Y., Joo, K.H., Lee, Y.H. Influence of calcium ion on host cell invasion and intracellular replication by Toxoplasma gondii, Korean J Parasitol. 42(4):185-193, 2004 https://doi.org/10.3347/kjp.2004.42.4.185
  12. 崔鎭瑞, 鄭坪林, 蘇鎭琸 Pyrimethamine이 [톡소프라스마]증에 미치는 영향에 관한 실험적 연구, Yonsei journal of medical science, 18(1):340-354, 1985
  13. Park, H., Kim, M.S., Jeon, B.H., Kim, T.K., Kim, Y.M., Ahnn, J.H., Kwon, D.Y., Takaya, Y., Wataya, Y., Kim, H.S. Antimalarial activity of herbal extracts used in traditional medicine in Korea, Biol Pham Bull. 26(11):1623-1624, 2003 https://doi.org/10.1248/bpb.26.1623