Our review has some limitations that have to be mentioned

known to bind at the top and one side of beta tubulin respectively. These binding sites, distinct 22223206 from the colchicine as well as curcumin binding site at the interface of the tubulin dimer, could explain the effect of curcumin-paclitaxel and curcuminvinblastine combinations. In the latter case curcumin and vinblastine, both destabilizing drugs, bind to two separate sites on the beta tubulin and bring about a synergistic effect in reducing the parasitemia. When combined with paclitaxel, curcumin shows an additive effect. This could be partly because paclitaxel and curcumin have two opposing modes of action on tubulin. However, the growth curves for combinations of these two drugs suggest that paclitaxel is the more potent partner in this combination and seems to be mostly responsible for the observed additive effect. Effect of curcumin on SB-590885 biological activity microtubules is more pronounced in the second cycle and associated with an altered apicoplast morphology The microtubule 19239230 disrupting action of curcumin becomes prominent in the second cycle. 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. Alternatively, it might be due to the fact that rings are less permeable in their uptake of external compounds. However, neither reason explains why some parasites escape the action of the drug even after the second cycle, at lower concentrations. An alternative explanation could be that curcumin, like the antibacterial agents tetracycline, azithromycin, ciprofloxaxin, doxycycline and clindamycin, exhibit its effect more prominently in the second cycle. A widely accepted model of the tetracycline mechanism of action in P. falciparum is based on loss of apicoplast function. Presently, no evidence has been cited in favor of an interaction between the apicoplast and microtubules in P. falciparum. However, in a related apicomplexan parasite, T. gondii, division and segregation of apicoplast into daughter cells have been observed to be linked with centrosomes/microtubules. It is possible that the disruption of microtubules seen after curcumin treatment causes a cascading effect which, in addition to disrupting schizogony, also disrupts apicoplast segregation and function. When treated with curcumin, parasites showed apicoplast morphology different from the untreated controls at same time points. Based on observations in T. gondii, tubular, undivided apicoplasts might have been expected in the mature stages resulting from a segregation defect. Instead diffuse apicoplast fluorescence is observed in the mature stages of treated parasites compared to discrete spherical apicoplasts found in daughter merozoites in Curcumin CI 48 hours Colchicine Paclitaxel Vinblastine 6.757 1.031 0.559 96 hours 2.513 1.422 0.919 CI 48 hours ND 1.645 1.640 96 hours ND 1.036 0.555 ND not determined: SFIC90 for curcumin-colchicine combination could not be determined because the maximum growth inhibition of treated parasites, even after 96 hours, was 35%.Plasmodium falciparum Microtubules and Curcumin untreated controls. This pattern of diffuse apicoplast fluorescence could also be a result of defective import of apicoplast proteins as has been reported previously with delayed death drugs. It is also possible that curc