Synthesis and Antimalarial Activity Evaluation of Some Mannich Bases of Tetraoxane-Phenol Conjugate

Abstract

A new series of seven Mannich bases of tetraoxane-phenol conjugate as possible antimalarial compounds were synthesized and evaluated in vitro for their antimalarial activity. All the synthesized compounds exhibited good antimalarial activity against the CQ-sensitive strain (RKL-2) of P. falciparum. Compounds with 3-indolyl and phenolic substituent’s showed considerably superior activity than rest of the synthesized tetraoxane derivatives in the series, with IC50 values 8.19 µg/ml and 5.30 µg/ml, respectively. The activity was, however, less than that of the standard reference drug, CQ (IC50 0.04 µg/ml). Three selected compounds were also screened for the activity against a CQ resistant strain (RKL-9) of P. falciparum, which was also found good with IC50 values 41.77 µg/ml, 39.87 µg/ml and 34.59 µg/ml for compounds having phenyl, furan-2-yl and 4-pyridyl substituent’s, respectively in the Mannich base component of the conjugated tetraoxane-phenol scaffold. The activity against CQ-sensitive strain of P. falciparum was better as compared to the activity seen against resistant strain. Results clearly indicate that Mannich bases of tetraoxane-phenol conjugate with bulky aromatic/heteroaromatic groups possess antimalarial potential both against CQ-sensitive and –resistant strains of P. falciparum.

Keywords: Mannich base; Tetraoxane; Endoperoxide; Plasmodium falciparum; Resistant; malaria