TY - JOUR
T1 - Effects of cinnamic acid derivatives on in vitro growth of Plasmodium falciparum and on the permeability of the membrane of malaria-infected erythrocytes
AU - Kanaani, J.
AU - Ginsburg, H.
PY - 1992
Y1 - 1992
N2 - Cinnamic acid derivatives (CADs) are known inhibitors of monocarboxylate transport across plasma and mitochondrial membranes. All derivatives were found to inhibit the growth of intraerythrocytic Plasmodium falciparum in culture, which is in correlation with their hydrophobic character. Parasites at the ring and trophozoite stages were equally susceptible to the different derivatives. This result could be attributed to their inhibition of the transport of lactate, the major product of parasite energy metabolism. However, unexpectedly, it was found that all derivatives also inhibit the translocation of carbohydrates and amino acids across the new permeability pathways induced in the host cell membrane by the parasite. This impediment correlated strictly with CADs' effect on parasite growth. Parasites residing in cells permeabilized by means of Sendai virus were less susceptible to the different drugs, a result which implies that in addition to the direct effect on parasite viability, the drugs may have inhibited some process in the host cell whose function may be vital for parasite growth. The effect of CADs on the ATP levels in infected cells, in virus-treated cells, and in the two cellular compartments of the infected cell revealed that the drugs caused a significant decline in ATP level in the parasite compartment, while they provoked only a small effect on ATP level in the intact cells and the host cell compartment. These observations suggest that CADs inhibit ATP production in the parasite and its utilization by the host cell.
AB - Cinnamic acid derivatives (CADs) are known inhibitors of monocarboxylate transport across plasma and mitochondrial membranes. All derivatives were found to inhibit the growth of intraerythrocytic Plasmodium falciparum in culture, which is in correlation with their hydrophobic character. Parasites at the ring and trophozoite stages were equally susceptible to the different derivatives. This result could be attributed to their inhibition of the transport of lactate, the major product of parasite energy metabolism. However, unexpectedly, it was found that all derivatives also inhibit the translocation of carbohydrates and amino acids across the new permeability pathways induced in the host cell membrane by the parasite. This impediment correlated strictly with CADs' effect on parasite growth. Parasites residing in cells permeabilized by means of Sendai virus were less susceptible to the different drugs, a result which implies that in addition to the direct effect on parasite viability, the drugs may have inhibited some process in the host cell whose function may be vital for parasite growth. The effect of CADs on the ATP levels in infected cells, in virus-treated cells, and in the two cellular compartments of the infected cell revealed that the drugs caused a significant decline in ATP level in the parasite compartment, while they provoked only a small effect on ATP level in the intact cells and the host cell compartment. These observations suggest that CADs inhibit ATP production in the parasite and its utilization by the host cell.
UR - http://www.scopus.com/inward/record.url?scp=0026710029&partnerID=8YFLogxK
U2 - 10.1128/AAC.36.5.1102
DO - 10.1128/AAC.36.5.1102
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C2 - 1510401
AN - SCOPUS:0026710029
SN - 0066-4804
VL - 36
SP - 1102
EP - 1108
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 5
ER -