Effects of Cryptolepine, 2, 7, dibromocryptolepine and standard drugs on hemoglobin accumulation in cultured Malaria parasites

Abstract

Cryptolepine is the major alkaloidal constituent of the West African climbing shrub Cryptolepis sanguinolenta, a species used in traditional medicine for the treatment of malaria and a number of other infectious diseases. Cryptolepine and a number of its synthetic analogues have been shown to have potent antiplasmodial activities using P. falciparum lactate dehydrogenase assay (PfLDH). Intraerythrocytic malaria parasites degrade host erythrocyte hemoglobin as a principal source of free amino acids for protein synthesis (Scheibel and Sherman, 1988). The accumulation of undigested hemoglobin in compounds and drug-treated infected cells in conjunction with inhibition of parasite growth has been studied in order to get a deeper insight into the mode of action of cryptolepine and its derivatives. The observation that cryptolepine inhibits the formation of b-haematin suggests that the antiplasmodial activity of cryptolepine appears to be due, at least in part, to a chloroquine-like action (Wright et al., 2001). Here it was found, using SDS-PAGE, that CQ could inhibit hemoglobin degradation, which is consistent with previous work (Orjih et al, 1994; Famin and Hagai 2002). We also showed that cryptolepine, 2, 7-dibromocryptolepine and amodiaquine (AQ), behave similarly. In contrast, quinine (Q) and mefloquine (MQ) did not affect this process. These results suggest that the antimalarial mode of action of cryptolepine and most probably its derivatives may inhibit the hemoglobin degradation process as a part of their parasite killing mechanism.