scaffolds and their possible targets.
2. LIFE CYCLE OF THE MALARIA PARASITE:
LIVER AND BLOOD STAGES
In (Fig 1), a pictorial view of the asexual stages: sporozoites, liver (exoerythrocytic stages) and blood stage (erythrocytic stage) of the P. falciparum life cycle inside the human host, is illustrated. During feeding, the infected female
Anopheles mosquito exposes the sporozoites to the human
blood circulation. The sporozoites move to the liver via
blood and stay in the hepatocytes (the liver cells) for 7-10
days [14]. Within the hepatocytes, the sporozoites multiply
into schizont and produce approximately 100,000 of merozoites resulting in the final rupturing and releasing of daughter parasites (merozoites). These merozoites enter into the
human bloodstream invading erythrocytes and hence giving
rise to ring stage. In the ring stage, the merozoites invade
more and more red blood cells and further replicate into enlarged ring shape trophozoites in the RBCs [15]. Trophozoites exhibit high metabolic activity, having rapid hemoglobin
catabolism. After several asexual cycles, some of the merozoites do not proceed to become trophozoites but instead
develop a sexual form known as gametocytes. These gametocytes are consumed by a mosquito through another blood
meal [35]. This process repeats itself completing the life cycle of P. falciparum. Each stage of the P. falciparum life
cycle opens the scope for a drug target. This article covers
the efficacy of the antimalarial drugs potent against both BS
and LS of Plasmodium parasites.
Fig. (1). Schematic representation of the liver and blood stages of
the P. falciparum life cycle inside the human body.
3. COMPOUNDS WITH POTENTIAL TO INHIBIT
LIVER AND BLOOD STAGE MALARIAL INFECTION
3.1. Compounds Isolated from Medicinal Plants
Natural products like quinine and artemisinin have been
significantly used as antimalarial agents [36]. Likewise,
Maria-José U. Ferreira and her group worked on the isolation
of Momordica balsamina L. (Cucurbitaceae), identified as
the African pumpkin or the balsam apple. It is widely used in
the subtropical and tropical regions of the world [37]. They
have isolated sixteen triterpenoids from this medicinal plant
study their efficacy against LS of P. berghei [38]. They have
also determined the luminescence intensity in Huh7 cells
infected with a firefly luciferase expressing P. berghei line,
PbGFP-Luccon, and against the blood stages of chloroquine-resistant clone Dd2 and chloroquine-sensitive strain
3D7 of P. falciparum [39]. Thus, illustrating their role as
dual stage inhibitors. On the same cell line, the toxicity of
these compounds was checked by the fluorescence measurement of the cell confluency. Karavoate B (1), a derivative
having two acetyl residues displayed the highest antimalarial
activity at the minimum concentration i.e. 1 µM, without any
toxicity towards the Huh7 cells. The reduction in the P. berghei infection was based on the dose-dependent rate. Karavoate B (1), is also a powerful inhibitor of BS of P. falciparum, therefore displays a dual-stage antimalarial activity.
In erythocytic stages of P. falciparum, triacetylbalsaminol F (2) exhibited the highest antiplasmodial activity (IC50:
0.2 µM, Dd2; 0.4 µM, 3D7). In addition, minimal cytotoxicity (IC50> 133.3 µM) was displayed by derivative 2. Apart
from this, a greater SI value was found for 2 (SI >342.9 and
162.4 for PfDd2 and Pf3D7 strains, respectively). Compound
2 was also displayed the superior antiplasmodial activity