Carbon nanospheres conjugated bisphosphonates: synthesis, characterization and in vitro antimalarial activity

Abstract

About 40% of the world’s population lives in malaria zones where it presents a challenging health problem. Malaria treatment and prevention have been hindered by drug resistance. Bisphosphonates have been found to be active against Trypanosoma cruzi and Plasmodium falciparum that cause Chaga’s disease and malaria respectively. However, bisphosphonates have a shortcoming of being rapidly removed from the bloodstream through the kidneys before reaching the target sites due to their low molecular weight. In the current study, increased bisphosphonates’ efficacy for malaria treatment was attempted by conjugating bisphosphonates onto carbon nanospheres (CNSs). The synthesis of the target compounds was confirmed by SEM, TEM, EDX, FTIR, Raman and TGA. The target CNSs containing bisphosphonates were evaluated for antimalarial activity against a chloroquine-resistant strain of P. falciparum. From the free bisphosphonates to the conjugates, the results obtained revealed that there were improvements in percentage parasite kill (from –10.71% to 18%, –18.93% to 28.09% and 10.47% to 28.33% for alendronate, pamidronate and neridronate, respectively). The haemolysis assays revealed that the synthesized compound did not have a toxic impact on healthy red blood cells. The results indicate that bisphosphonates conjugated CNSs are said to be promising P. falciparum blood stage inhibitors.