Synthesis and characterization of water-soluble polyaspartamides containing platinum(II) complex and bisphosphonate as potential antimalarial drug

Polyaspartamides conjugates and co-conjugates containing platinum(II) complex and bisphosphonate were synthesized by stepwise reaction of polysuccinimide with selected primary amines. The first step was achieved by aminolytic ring opening of polysuccinimide and afforded conjugates containing bisphosphonate and dihydroxylato ligand for platinum chelation. In the second step conjugates were chelated to platinum(II) complex. These conjugates and co-conjugates were characterized by proton and phosphorus nuclear magnetic resonance (H-1 and P-31 NMR), Fourier transform spectroscopy (FTIR), scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDX). The mass percentage incorporation of platinum in the co-conjugates was determined by ICP-OES and was found to be between 1.9 and 3.7 percent, while the mass percentage incorporation of bisphosphonate in the conjugates and co-conjugates was found to be between 2.5 and 3.1 percent by NMR. The preliminary pharmacological evaluation performed on co-conjugates 4, 5 and 6 revealed that co-conjugate 6 exhibited enhanced antimalarial activity than chloroquine, while co-conjugates 4 and 5 were less active.