Mitotic inhibitors arrest the growth of Plasmodium falciparum

Abstract

We report that the mitotic inhibitor, vinblastin (VLB), is highly toxic to the malarial parasite, Plasmodium falciparum. In cultures in vitro growth is inhibited by SO$ at a VLB level of about 28 nM, and totally abolished at a level of 100 nM. By tests on synchronized cultures we have found that the effect of VLB takes place at the trophozoite stage. Colcemid also inhibits schizogony with somewhat different kinetics. By mutagenesis with nitrosoguanidine followed by VLB selection we have isolated a VLB-resistant mutant which exhibits cross-resistance to vincristine. These data suggest a critical role of microtubules in the asexual schizogonic cycle of P. falciparum. Malaria(P. falciparum) Vinblastine Tub&n

Interactions between docetaxel (Taxotere) and Plasmodium falciparum-infected erythrocytes.

“…7 and this study) or Colcemid (7). They are in the same range as those observed with the vinca alkaloids, vinblastine and vincristine (6,7). In contrast to Taxotere, these latter drugs inhibit the polymerization of tubulin into microtubules and also interfere with neuronal transport resulting in pronounced neurotoxicity, which is reversible (21,22).…”

“…The chronology of the erythrocytic schizogony (4) and its experimental induction (5) are well known, but the molecular cascades that mediate each step are poorly understood. Few studies with antimicrotubule drugs that depolymerize microtubules have focused on P. falciparum (6,7).…”

Cellular Effects of Curcumin on Plasmodium falciparum Include Disruption of Microtubules

“…This delayed aspect of its action may be attributed to several possible factors. If curcumin acts stage specifically in the mature parasites and considering a tight 100% synchrony is hard to achieve, it might be possible for some parasites to escape the drug action in the first cycle as has been observed previously with vinblastine [26]. Alternatively, it might be due to the fact that rings are less permeable in their uptake of external compounds [35].…”

“…These include microtubule stabilizing agents - taxoids [22], [23] and various destabilizing agents - colchicum alkaloids [24], [25], vinca alkaloids [26], dinitroanilines [27] and tubulozoles [28], [29]. The effects of microtubule inhibition by these compounds on the erythrocytic cycle of P. falciparum have been suggested due to defects in cellular processes that are thought to be dependent on microtubule function: merozoite formation [23], inhibition of invasion of erythrocytes by daughter merozoites [25] and blocking of nuclear division [22].…”

Malaria Hidden in a Patient with Diffuse Large-B-Cell Lymphoma and Sickle-Cell Trait

“…During the 20-month period of disease progression (Fig. 2), the immunoreactivity of the patient's serum against his own schizonts revealed that specific antibodies had significantly decreased after his initial arrival in Spain, probably due either to gradually impaired parasite growth since some drugs used for the lymphoma treatment (e.g., vincristine) are known to inhibit P. falciparum growth (21) or to the waning of natu- rally acquired immunity as a consequence of staying outside the area of endemicity (11). Thus, the rise in specific antibodies detected after the patient's trip to Africa seems to indicate malaria reinfection.…”