Synthesis by Click Reactions and Antiplasmodial Activity of Lupeol 1,2,3-Triazole Derivatives

Abstract

Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity lupeol derivatives, five new 1,2,3-triazole hybrid molecules were synthetized by copper-catalyzed azide-alkyne cycloaddition. The antiplasmodial activity of the semi-synthetic compounds were evaluated by the lactate dehydrogenase assay; the lupeol propargyl ether was the only one to disclosing increased activity (half maximal inhibitory concentration-IC 50 -62.0 ± 1.92 μmol L ). Therefore, this work revealed a new class of interesting lupeol derivatives that can be obtained by linking electron donors to the hydroxy group at C-3.

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits

“…All of the HNQs ( 6a–h ), ortho- FNQs ( 7a–h ), and para -FNQs ( 8a–h ) were classified as in vitro antiplasmodial active compounds (parasitemia reduction > 50% at 25 μ g·mL −1 ), and their IC 50 values were experimentally determined by the p LDH methodology ( Table 2 ) [ 40 , 42 ]. Lawsone glycidyl ether ( 9 ) and ANQs ( 10a–c ) were inactive, with parasitemia reduction ranging from 9% to 34% at 25 μ g·mL −1 ( Table 1 ); therefore, their IC 50 and CC 50 were not determined.…”

“…There are several in vitro methods commonly used for the assessment of parasite growth inhibition [ 38 ]. The parasite protein lactate dehydrogenase ( p LDH) method [ 39 , 40 ] was chosen to evaluate the in vitro antiplasmodial activity of HNQs 6a–h , ortho- FNQs 7a–h , 8a–h , 9 , and ANQs 10a–c.…”

“…Stock solutions at 50 mg·mL −1 of each compound in DMSO were diluted in a complete medium, in serial concentrations of 2 : 1 to final concentrations of 0.002% (v/v), and 20 μ l of each one was added to the 96-well culture plates containing the parasite culture. After 48 h incubation, the plates were frozen (−20°C for 24 h) and thawed before starting the p LDH assay [ 40 ].…”

“…After 24 h incubation at 37°C, 28 µ L of MTT solution (2 mg·mL −1 in PBS) was added to each well. After 1.5 h of incubation at 37°C, the supernatant was removed and 130 µ L of DMSO was added to each well [ 40 , 42 ]. The experiment was performed three times, each one in triplicate.…”