Abstract
Protozoal infections caused by species belonging to
complex are responsible for the most severe form of leishmaniasis, especially in Sudan and other developing countries. Drugs commonly used for the treatment of the disease show varying levels of effectiveness and also have associated side effects. Thus, the present work highlights the synthesis of some chalcones to be used as potential anti-leishmanial agents. The activity of the synthesized chalcones has been evaluated against
.
. The ADMET profile of the synthesized compounds were tested using various integrated web-based tools. Moreover, in order to investigate the molecular mechanism of action, the chalcone compounds were docked into
.
trypanothione reductase (TR) using Autodock 4.0 and molecular dynamics were studies. Eight compounds showed the highest activity against the morphological forms. Among these compounds, chalcones
has shown the highest inhibitory effect with IC
value of 1.1 µM. In addition, pharmacokinetic and toxicological investigations revealed its good oral bioavailability and low toxicity. Furthermore, chalcone
was found to interact with high affinity (−13.7 kcal/mol) with TR, an essential enzyme for the leishmanial parasite. Thus, this promising activity against
.
supports the use of chalcone
as a potential new therapy for visceral leishmaniasis.