Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-22T00:07:42.510Z Has data issue: false hasContentIssue false
  • English
  • Français

Activity of benzothiazoles and chemical derivatives on Plasmodium falciparum

Published online by Cambridge University Press:  05 October 2004

S. HOUT ,
N. AZAS ,
A. DARQUE ,
M. ROBIN ,
C. DI GIORGIO ,
M. GASQUET ,
J. GALY  and
P. TIMON-DAVID
S. HOUT
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
N. AZAS
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
A. DARQUE
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
M. ROBIN
Affiliation:
Laboratoire de Valorisation de la Chimie Fine, Université d'Aix-Marseille III, site de Saint Jérome, Marseille, France
C. DI GIORGIO
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
M. GASQUET
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
J. GALY
Affiliation:
Laboratoire de Valorisation de la Chimie Fine, Université d'Aix-Marseille III, site de Saint Jérome, Marseille, France
P. TIMON-DAVID
Affiliation:
Laboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd Jean Moulin, Marseille cedex 05, France
Get access Rights & Permissions [Opens in a new window]

Abstract

Malaria is a major health concern particularly in Africa which has about 90% of the worldwide annual clinical cases. The increasing number of drug-resistant Plasmodium falciparum justifies the search for new drugs in this field. Antimalarial activity of 2-substituted 6-nitro- and 6-amino-benzothiazoles and their anthranilic acids has been tested. An in vitro study has been performed on W2 and 3D7 strains of P. falciparum and on clinical isolates from malaria-infected patients. Toxicity has been assessed on THP1 human monocytic cells. For the most active drug candidates, the in vitro study was followed by in vivo assays on P. berghei-infected mice and by in vitro assays in order to determine the stage-dependency and the mechanism of action. Of 39 derivatives tested in vitro, 2 had specific antimalarial properties. Each compound was active on all stages of the parasite, but one was markedly active on mature schizonts, while the other was more active on young schizont forms. Both drugs were also active on mitochondrial membrane potential. In vivo data confirmed efficiency with a sustained decrease of parasitaemia. Products A12 and C7 may be considered as potential antimalarial worthy of further chemical and biological research.

Keywords

malariabenzothiazolesPlasmodium falciparummechanism of action
Type
Research Article
Information
Parasitology , Volume 129 , Issue 5 , November 2004 , pp. 525 - 542
Copyright
© 2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

AGER, A. ( 1984). Rodent malarial models. In Antimalarial Drugs. I. Biological Background, Experimental Methods and Drug Resistance (ed. Peters, W. & Richards, W. H. G.), pp. 225–264. Springer-Verlag, Berlin, Germany.
ALBERTS, B., BRAY, D., LEWIS, J., RAFF, M., ROBERTS, K. & WATSON, J. ( 1994). Molecular Biology of the Cell, pp. 665–683. Garland, New York.
AUPARAKKITANON, S. & WILAIRAT, P. ( 2000). Cleavage of DNA induced by 9-anilinoacridine inhibitors of topoisomerase II in the malaria parasite Plasmodium falciparum. Biochemical and Biophysical Research Communications 269, 406–409.CrossRefGoogle Scholar
AZAS, N., LAURENCIN, N., DELMAS, F., DI GIORGIO, C., GASQUET, M., LAGET, M. & TIMON-DAVID, P. ( 2002). Synergistic in vitro antimalarial activity on plant extracts used as traditional herbal remedies in Mali. Parasitology Research 88, 165–171.CrossRefGoogle Scholar
BAE, H., LEE, Y., KANG, D., KOO, J., YOON, B., ROH, J. & GU, J. ( 2000). Neuroprotective effect of low dose riluzol in gerbil model of transient global ischemia. Neuroscience Letters 294, 29–32.CrossRefGoogle Scholar
BASCO, L. & RINGWALD, P. ( 2000). Molecular epidemiology of malaria in Yaounde, Cameroun. VII. Analysis of recrudescence and reinfection in patients with uncomplicated falciparum malaria. American Journal of Tropical Medicine and Hygiene 63, 215–221.Google Scholar
BRADSHAW, T., WRIGLEY, S., SHI, D., SCHULTZ, R., PAULL, K. & STEVENS, M. ( 1998). 2-(4-Aminophenyl)-benzothiazoles: novel agents with selective profiles of in vitro anti-tumour activity. British Journal of Cancer 77, 745–752.CrossRefGoogle Scholar
BURRES, N., FRIGO, A., RASMUSSEN, R. & McALPINE, J. ( 1992). A colorimetric microassay for the detection of agents that interact with DNA. Journal of Natural Products 55, 1582–1587.CrossRefGoogle Scholar
CASSILETH, P. & GALE, R. ( 1986). Amsacrine: a review. Leukemia Research 10, 1257–1265.CrossRefGoogle Scholar
CHUA, M., SHI, D., WRIGLEY, S., BRADSHAW, T., HUTCHINSON, I., SHAW, P., BARRETT, D., STANLEY, L. & STEVENS, M. ( 1999). Antitumor benzothiazoles. 7. Synthesis of 2-(4-acylaminophenyl) benzothiazoles and investigations into the role of acetylation in the antitumor activities of the parent amines. Journal of Medicinal Chemistry 42, 381–392.Google Scholar
COX, F. ( 1988). Major animal models in malarial research: rodent. In Malaria. Principles and Practice of Malariology (ed. Wernsdorfer, W. H. & McGregor, I.), pp. 1503–1543. Churchill Livingstone Ltd, Edinburgh, Scotland.
DELMAS, F., DI GIORGIO, C., ROBIN, M., AZAS, N., GASQUET, M., DETANG, C., COSTA, M., TIMON-DAVID, P. & GALY, J. P. ( 2002). In vitro activities of position 2 substitution-bearing 6-nitro- and 6-amino-benzothiazoles and their corresponding anthranilic acid derivatives against Leishmania infantum and Trichomonas vaginalis. Antimicrobial Agents and Chemotherapy 46, 2588–2594.CrossRefGoogle Scholar
DING, A., NATHAN, C. & STUEHR, D. ( 1988). Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. Journal of Immunology 141, 2407–2412.Google Scholar
EL-SHAAER, H., ABDEL-AZIZ, S., ALLIMONY, H., ALI, U. & ABDEL-RAHMAN, R. ( 1997). Synthesis and antimicrobial activities of some new 2-substituted benzoxazole/benzothiazole derivatives. Pharmazie 52, 585–589.CrossRefGoogle Scholar
FRY, M. & BEESLEY, J. ( 1991). Mitochondria of mammalian Plasmodium spp. Parasitology 102, 17–26.CrossRefGoogle Scholar
FRY, M. & PUDNEY, M. ( 1992). Site of action of the antimalarial hydroxynaptoquinone, 2-(trans-4-(4′-chlorophenyl)cyclohexyl)-3-hydroxy-1,4-nphtoquinone (566C80). Biochemical Pharmacology 43, 1545–1553.CrossRefGoogle Scholar
FRY, M., WEBB, E. & PUDNEY, M. ( 1990). Effect of mitochondrial inhibitors on adenosine triphosphate levels in Plasmodium falciparum. Comparative Biochemistry and Physiology B 96, 775–782.Google Scholar
GAMAGE, S., FIGGITT, D., WOJCIK, S., RALPH, R., RANSIJN, A., MAUEL, J., YARDLEY, V., SNOWDON, D., CROFT, S. & DENNY, W. ( 1997). Structure-activity relationships for the antileishmanial and antitrypanosomal activities of 1′-substituted 9-anilinoacridines. Journal of Medicinal Chemistry 40, 2634–2642.CrossRefGoogle Scholar
GOLDRING, J. & NEMAORANI, S. ( 1999). Antimalarial drugs modulate the expression of monocyte receptors. International Journal of Immunopharmacology 21, 599–607.CrossRefGoogle Scholar
HEIFFER, M., DAVIDSON, D. & KORTE, D. ( 1984). Preclinical testing. In Antimalarial Drugs. I. Biological Background, Experimental Methods and Drug Resistance (ed. Peters, W. & Richards, W. H. G.), pp. 351–373. Springer-Verlag, Berlin, Germany.
JONCKERS, T., VAN MIERT, S., CIMANGA, K., BAILLY, C., COLSON, P., DE PAUW-GILLET, M., VAN DEN HEUVEL, H., CLAEYS, M., LEMIERE, F., ESMANS, E., ROZENSKI, J., QUIRIJNEN, L., MAES, L., DOMMISSE, R., LEMIERE, G., VLIETINCK, A. & PIETERS, L. ( 2002). Synthesis, cytotoxicity, and antiplasmodial and antitrypanosomal activity of new neocryptolepine derivatives. Journal of Medicinal Chemistry 45, 3494–3508.CrossRefGoogle Scholar
KENNEL, P., REVAH, F., BOHME, G., BEJUIT, R., GALLIX, P., STUTZMANN, J., IMPERATO, A. & PRATT, J. ( 2000). Riluzole prolongs survival and delays muscle strength deterioration in mice with progressive motor neuropathy. Journal of the Neurological Sciences 180, 55–61.CrossRefGoogle Scholar
KRUNGKRAI, S. & YUTHAVONG, Y. ( 1987). The antimalarial action on Plasmodium falciparum of qinghaosu and artesunate in combination with agents which modulate oxidant stress. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 710–714.CrossRefGoogle Scholar
LAMBROS, C. & VANDERBERG, I. ( 1979). Synchronization of Plasmodium falciparum erythrocytic stages in culture. Journal of Parasitology 65, 418–420.CrossRefGoogle Scholar
LEONG, C., GASKELL, M., MARTIN, E., HEYDON, R., FARMER, P., BIBBY, M., COOPER, P., DOUBLE, J., BRADSHAW, T. & STEVENS, M. ( 2003). Antitumour 2-(4-aminophenyl)benzothiazoles generate DNA adducts in sensitive tumour cells in vitro and in vivo. British Journal of Cancer 88, 470–477.CrossRefGoogle Scholar
MESHNICK, S., YANG, Y., LIMA, V., KUYPERS, F., KAMCHONWONGPAISAN, S. & YUTHAVONG, Y. ( 1993). Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu). Antimicrobial Agents and Chemotherapy 37, 1108–1114.CrossRefGoogle Scholar
NOGRADI, A. & VRBOVA, G. ( 2001). The effect of riluzole treatment in rats on the survival of injured adult and grafted embryonic motorneurons. European Journal of Neuroscience 13, 113–118.CrossRefGoogle Scholar
OGUNKOLADE, B., COLOMB-VALET, I., MONJOUR, L., RHODES-FEUILLETTE, A., ABITA, J. & FROMMEL, D. ( 1990). Interactions between the human monocytic leukemia THP1 cell line and Old and New World species of Leishmania. Acta Tropica 47, 171–176.CrossRefGoogle Scholar
PARAPINI, S., BASILICO, N., PASINI, E., EGAN, T., OLLIARO, P., TARAMELLI, D. & MONTI, D. ( 2000). Standardization of the physicochemical parameters to assess in vitro the beta-hematin inhibitory activity of antimalarial drugs. Experimental Parasitology 96, 249–256.CrossRefGoogle Scholar
PETERS, W., ROBINSON, B., TOVEY, G., ROSSIER, J. & JEFFORD, C. ( 1993). The chemotherapy of rodent malaria. The activities of some synthetic 1,2,3-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 3: observation on ‘Fenozan-50F’, a difluorinated 3,3′-spirocyclopentane 1,2,4-trioxane. Annals of Tropical Medicine and Parasitology 87, 111–123.Google Scholar
PRADINES, B., ROLAIN, J., RAMIANDRASOA, F., FUSAI, T., MOSNIER, J., ROGIER, C., DARIES, W., BARET, E., KUNESCH, G., LE BRAS, J. & PARZY, D. ( 2002 a). Iron chelators as antimalarial agents: in vitro activity of dicatecholate against Plasmodium falciparum. Journal of Antimicrobial Chemotherapy 50, 177–187.Google Scholar
PRADINES, B., TALL, A., ROGIER, C., SPIEGEL, A., MOSNIER, J., MARRAMA, L., FUSAI, T., MILLET, P., PANCONI, E., TRAPE, J. & PARZY, D. ( 2002 b). In vitro activities of ferrochloroquine against 55 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Tropical Medicine and International Health 7, 265–270.Google Scholar
RANE, D. & KINNAMON, K. ( 1979). The development of a ‘high volume tissue schizonticidal drug screen’ based upon mortality of mice inoculated with sporozoites of Plasmodium berghei. American Journal of Tropical Medicine and Hygiene 28, 937–947.CrossRefGoogle Scholar
SLATER, A., SWIGGARD, W., ORTON, B., FLITTER, W., GOLDBERG, D., CERAMI, A. & HENDERSON, G. ( 1991). An iron-carboxylate bond links the heme units of malaria pigment. Proceedings of the National Academy of Sciences, USA 88, 325–329.CrossRefGoogle Scholar
SRIVASTAVA, I., ROTTENBERG, H. & VAIDYA, A. ( 1997). Atovaquone, a broad spectrum antiparasitic drug, collapses mitochondrial membrane potential in a malarial parasite. Journal of Biological Chemistry 272, 3961–3966.CrossRefGoogle Scholar
TRAGER, W. & JENSEN, J. ( 1976). Human malaria parasites in continuous culture. Science 193, 673–675.CrossRefGoogle Scholar
TRAORE-KEITA, F., GASQUET, M., DI GIORGIO, C., OLLIVIER, E., DELMAS, F., KEITA, A., DOUMBO, O., BALANSARD, G. & TIMON-DAVID, P. ( 2000). Antimalarial activity of four plants used in traditional medicine in Mali. Phytotherapy Research 14, 45–47.3.0.CO;2-C>CrossRefGoogle Scholar
TRAPANI, G., LATROFA, A., FRANCO, M., ARMENISE, D., MORLACCHI, F. & LISO, G. ( 1994). Synthesis and antimicrobial activity of some N-alkenyl-2-acylalkylidene-2,3-dihydro-1,3-benzothiazoles. Arzneimittelforschung 44, 969–971.Google Scholar
VAN DER HEYDE, H., ELLOSO, M., VAN DE WAA, J., SCHELL, K. & WEIDANZ, W. ( 1995). Use of hydroethidine and flow cytometry to assess the effect leukocytes on malarial parasite. Clinical and Diagnostic Laboratory Immunology 2, 417–425.Google Scholar
WAHLGREN, M., BERZINS, K., PERLMANN, P. & BJORKMAN, A. ( 1983). Characterization of the humoral immune response in Plasmodium falciparum malaria. I. Estimation of antibodies to P. falciparum or human erythrocytes by means of microELISA. Clinical and Experimental Immunology 54, 127–134.Google Scholar
WHITEHEAD, S. & PETO, T. ( 1990). Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro. Blood 76, 1250–1255.Google Scholar
WORLD HEALTH ORGANIZATION. Expert committee on malaria – 20th report. Available at http://mosquito.who.int/docs/ecr20_2.htm on November 2003.
YAYON, A., VAN DE WAA, J., YAYON, M., GEARY, T. & JENSEN, J. ( 1983). Stage-dependent effects of chloroquine on Plasmodium falciparum in vitro. Journal of Protozoology 30, 642–647.CrossRefGoogle Scholar