Synthesis and Antimalarial Activity Assay of <i>C</i>- Arylcalix[4]pyrogallolarenes Using Heme Polymerization Inhibition Activity (HPIA) Method

Abstract

Malaria is one of the most devastating and widespread tropical parasitic diseases in developing countries with high prevalence. Furthermore, antimalarial drug resistance results in a global resurgence of malaria. Thus there is an urgent need to find new and active antimalarial agents. In this work, we reported the synthesis of C-arylcalix[4]pyrogallolarenes and their in vitro activity assay as new antimalarial agent candidates. The C-arylcalix[4]pyrogallolarenes were prepared in high yields through a condensation reaction between pyrogallol and aromatic aldehydes (i.e., benzaldehyde, 4-hydroxy-3-methoxybenzaldehyde, and 2-chlorobenzaldehyde) under acidic conditions. The antimalarial activity of C-arylcalix[4]pyrogallolarenes was tested using the Heme Polymerization Inhibition Activity (HPIA) method with chloroquine diphosphate as the positive control. The heme polymerization inhibitory activity was reflected from the IC50 values in which the IC50 values were obtained from probit analysis using IBM SPSS statistics 25 software. The result showed that the IC50 values of C-arycalix[4]pyrogallolarene derivatives were in a range of 0.238–1.268 mg/mL, which were lower than chloroquine diphosphate (IC50 = 2.788 mg/mL). This finding reveals that the C-arylcalix[4]pyrogallolarenes are potential antimalarial agents to be developed in the future.