Synthesis of [²H]‐ and [¹³C]‐labeled pyronaridine tetraphosphate—an antimalarial drug

Abstract

The increasing prevalence of strains of Plasmodium falciparum resistant to chloroquine and other antimalarial drugs, necessitates the need for developing novel antimalarial drugs with a potent pharmacological activity. Pyronaridine tetraphosphate (PNDP) is one such drug that is currently undergoing preclinical and clinical trials for use in a chemotherapy treatment of malaria. The present investigation was carried out with the objective of synthesizing carbon-13 [13 C]-and deuterium [ 2 H]-labeled PNDP for use in studying the ADME and pharmacokinetics of the drug. Here, we present a methodology to synthesize [13 C]-and [ 2 H]-PNDP using a microwave irradiation technique as this method was found to be more advantageous than the classical method. The labeled compounds thus synthesized had a chemical purity of 499% as determined by HPLC and were also found to be relatively stable up to 3 months when stored under standard conditions. Further they also revealed satisfactory instrumental analysis data.