WIWIED EKASARI, 090710379 D (2010) IDENTIFIKASI TARGET BIOKIMIAWI SENYAWA ANTIMALARIA HASIL ISOLASI DAUN CASSIA SIAMEA LAMK. Disertasi thesis, UNIVERSITAS AIRLANGGA.

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Abstract

Isolation of the constituents of C. siamea Lamk leaves yielded cassiarin A,cassiarin B, anhydrobarakol and two unidentified isolates. In vitro assays of antimalarial activity of all isolates against P. falciparum 3D7 indicated that cassiarin A was the most active compound with IC50 of 0.001 μg/ml. In vivo assays of antimalarial activity of cassiarin A and chloroquine diphosphate against P. berghei infected mice showed that cassiarin A was more active than chloroquine diphosphate (ED50 0.17 and 0.21 mg/kg body weight), respectively. In vitro assay of cassiarin A against P. falciparum led to morphological alterations of ring form and trophozoites stages, as well as hemozoins. The growth of parasites was found slower than that untreated parasites. Ultrastructural analysis of parasites found only a small amount of hemozoin with irregular shape, some parasites showed no hemozoin at all, swelling of food vacuoles, increase in vesicle transport of hemoglobin, and lamellar formations. Identification of biochemical targets of cassiarin A by means of inhibition test of endocytosis processes, hemoglobin degradation and heme detoxification indicated that cassiarin A inhibited all those processes. But, inhibition of endocytotic process by cassiarin A in this experiment showed a higher activity than that of chloroquine diphosphate. The results indicated that C. siamea Lamk leaves possesses antimalarial activity was an active antimalarial both in vitro and in vivo against P. falciparum and P. berghei, as well as inhibiting endocytosis, hemoglobin degradation, and heme detoxification. Hence, cassiarin A has a high potential as candidate for novel antimalarials agent.

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