Chloroquine antimalarial activity

Navarro, M., Vasquez, F., Sanchez-Delgado, R.A., Perez, H., Sinou, V. and Schrevel, J. (2004) Toward a Novel Metal-Based Chemotherapy against Tropical Diseases. 7. Synthesis and in Vitro Antimalarial Activity of New Gold-Chloroquine Complexes. Journal of Medicinal Chemistry, 47, 5204. 

These complexes were tested for in vitro antimalarial activity showing that the coordination to the Au increases the potency of chloroquine. The ferrocenyl ligands... 

Blackie, M.A.L., Beagley, P., Chibale, K., Clarkson, C., Moss, J.R. and Smith, P.J. (2003) Synthesis and antimalarial activity in vitro of new heterobimetallic complexes Rh and Au derivatives of chloroquine and a series of ferrocenyl-4-amino-7-chloroquinolines. Journal of Organometallic Chemistry, 688(1-2), 144-152. 

Chloroquine is the drug of choice for preventing and treating acute forms of malaria caused by P. vivax, P. malariae, P ovale, as well as sensitive forms of P. falciparum. The mechanism of its action is not completely clear, although there are several hypotheses explaining its antimalarial activity. Chloroquine and its analogs inhibit synthesis of nucleic acids of the parasite by affecting the matrix function of DNA. This happens by preliminary... 

Chloroquine (Aralen) is one of several 4-aminoquino-line derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++-calmodulin-mediated mechanisms. It also accumulates in the parasite s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. 

In order to determine the significance of the 1,5-H shift and the secondary radical species for antimalarial activity, the trioxanes 22a—c were synthesized and tested18. The diastereomeric trioxanes 22a and 22b possessed very different antimalarial activity against both chloroquine-resistant and chloroquine-sensitive strains of the parasite the 4-/3 isomer was approximately twice as active as artemisinin while the 4-a isomer and the disubsti-tuted trioxane were more than sixty times less potent. The authors proposed that the (y-substitucnt prevented the suprafacial 1,5-H shift and therefore suppressed the activity of these compounds. 

A rapid semiautomated microdilution method for the microbiological assay of the chloroquine has been developed by Desgardins (26). Antimalarial activity of chloroquine may be studied against cultured Plasmodium falciparum, microplates are used to prepare serial dilution of the drug. Parasites obtained from continuous stock cultures are subcultured in the micro-plates for 42 h. Inhibition of uptake of a radio labeled nucleic acid precursor by parasites serves as the indicator of antimicrobial activity. 

Biot C, Glorian G, Maciejewski LA, Brocard JS (1997) Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue. J Med Chem 40 3715-3718... 

The compounds were tested against P. falciparum (3D7) and showed good antimalarial activity (Fig. 18). In particular, compounds 136 showed much better potency than chloroquine, a known antimalarial agent (MIC = 0.39 pg/mL). 

Malaria remains one of the most important diseases of humanity with over half of the world population at risk of infection. It affects mainly those living in tropical and subtropical areas with an incidence of 500 million cases per year globally. The antimalarial activity of 4-(5-trifluoromethyl-17/-pyrazol-l-yl)chloroquine analogues 875 has been evaluated in vitro against a chloroquine-resistant Plasmodium falciparum clone <2006BML649>. 

Drug activation by iron and heme may explain why endoperoxides are selectively toxic to malaria parasites. The malaria parasites live in a milieu of heme iron, which the parasite converts into insoluble hemozoin. Chloroquine, which binds heme, antagonizes the antimalarial activity of artemisinin. 

Ajoene, another garlic derivative, has exhibited antimicrobial activities (Yoshida et al., 1999) and, when used with chloroquine, has been shown to increase the antimalarial activity of chloroquine against the parasite P. berghei (Perez et al., 1994). 

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