Antiplasmodial drugs

A special problem arose with respect to the antiplasmodial drugs chloroquine (Resochin) and quinacrine (Atebrin). Plasmodia can not be propagated in cell-free lifeless media and the limited availability of erythrocytic plasmodial cultures severely limits biochemical or molecular pharmacological studies on the action of antimalarials. The actions of chloroquine and quinacrine were, therefore, studied in Bacillus megaterium or E. coli, respectively 22 ... 

Quinine (t) 9 h 18 h in severe malaria) is obtained from the bark of the South American Cinchona tree. It binds to plasmodial DNA to prevent protein synthesis but its exact mode of action remains uncertain. It is used to treat Plasmodium falciparum malaria in areas of multiple-drug resistance. Apart from its antiplasmodial effect, quinine is used for myotonia and muscle cramps because it prolongs the muscle refractory period. Quinine is included in dilute concentration in tonics and aperitifs for its desired bitter taste. 

Plants accumulate STLs as a means of chemical defence. Thus, one of the primary ecological benefits of these compounds is certainly the fact that they are toxic to all kinds of microorganisms. Once more it is their alkylant potency that is most obviously responsible. The work on antimicrobial activity of earlier years has been summarized in various reviews, e.g. [1-3]. More recent work has indicated that some STLs may have potential as leads for new antiprotozoal drugs. Apart from the prominent antimalarial artemisinin which will be treated separately in the following section, several more common STLs have been demonstrated to possess antiplasmodial [77-79], antileishmanial [80] and antitrypanosomal activity [81-84], Unfortunately, in most cases such activities are accompanied by high non-specific cytotoxicity so that it is always necessary to compare the antiprotozoal activity with cytotoxic effects determined under the same conditions. 

This number is an estimation of selective inhibition of P. falciparum by a test compound or extract. The SI value affords a qualitative measure of activity which may be compared empirically to those of known antimalarial drugs. The parameter is used to prioritize active test samples and to guide bioassay-directed fractionation with the aim of isolating the most promising antiplasmodial compounds. Selectivity indices have also been employed in the analysis of structure-activity relationships among a group of closely related compounds in an attempt to... 

Quassinoids are degraded triterpenes, reported from the members of the Simarouboidaea subfamily of Simaroubaceae. Legend states that a man named Quassi treated fever using the bitter extracts derived from the bark of these trees and hence named quassin [2]. Quassinoids have received attention due to their antiplasmodial, anticancer, and anti-HIV properties. Its efficacy as combinatorial drug coupled with the structure-activity analysis has reclaimed novel structural leads for new drug development. 

Compared with the plethoric studies on antiplasmodial activity against P. falciparum in vitro, in vivo antimalarial assays dedicated to quassinoids are scarce and hardly comparable. Nevertheless, the excellent antimalarial activities highlighted in those studies should open the way to complementary studies of their pharmacokinetics and toxicity. Association with other antimalarials should also be investigated in order to define new therapeutic schemes and to lower the administered doses, increasing drugs tolerability. 

Laconde, G., Bourin, A., Cos, P., Maes, X, and Deprez, B. (2011) Drug to genome to drug discovery of new antiplasmodial compounds. Journal of Medicinal Chemistry, M, 3222 3240. 

In chronic brucellosis, Brucella abortus infects macrophages, thus eluding the immune response [253]. When immunostimulatory drugs such as couma-rin were administered, the symptoms of chronic brucellosis disappeared. These results have encouraged the use of coumarin in other chronic infections such as mononucleosis (Epstein-Barr virus), mycoplasmosis (Mycoplasma pneumoniae), toxoplasmosis (Toxoplasma gondii), and Q fever (Coxiella burnetii). Also, another antiplasmodial coumarin derivate called 5,7-dimethoxy-8-(3 -hydroxy-3 methyl-l -butene)-coumarin has been isolated from the roots of the plant Toddalia asiatica. This finding supports the traditional use of this plant for the treatment of malaria [254]. 

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