Trihydroxyflavanone isolated from Dipteryx lacunifera Ducke (Fabaceae) as a potential antimalarial drug: An in silico and in vitro approach.

Dipteryx lacunifera is an example of the Brazilian cerrado flora which recently showed promising biological actions, such as antioxidant and antibacterial activities and a potential antimalarial effect. This study evaluated three flavonoids isolated from the fruits kernels of D. lacunifera, 7,3´, 4´-trihydroxyflavone (1), 7,3´,4´-trihydroxyflavanone (2), and (-)-eriodictyol (3). Virtual molecular modeling platforms (in silico), chemotherapy assays with P. falciparum W2 strain, and cytotoxicity assays (in vitro) were used to verify the antimalarial and cytotoxic potential of these molecules. Compound 2 showed the best results of inhibitory concentration against the P. falciparum W2 strain (IC50 = 7.35 μM), with low cytotoxicity against the human fibroblast lineage (WI- 26-VA4) (LC50 > 100 μM) and high selectivity index (IS = 13.61). In silico analysis of the mechanism of action of 2 was performed by selecting the 5 crystallographic complexes with the best binding energy, namely: 1O5X, 2OK8, 2VFA, 4C81, and 4N0Z, suggesting more than one mode of action. The compounds met the ADMET criteria, indicating good bioavailability results. These results may lead this molecule to be submitted to further studies.