Novel Imidazoquinoline Based TLR7 Agonist Induces Antileishmanial Efficacy-An In Vitro Study

Leishmaniasis elimination and control remain challenging due to the lack of successful treatment and possible prevention. A suitable anti-leishmanial medication that is acceptable in terms of price and safety is currently being researched. In light of this, the current study examined the effectiveness of imidazoquinoline based selective Toll-like receptor (TLR)-7 agonists as anti-leishmanial agents. A library of TLR7 agonists was evaluated for anti-leishmanial efficacy against experimental visceral leishmaniasis (VL). Among all the agonists, 2-butyl-1-(3,4-dimethoxybenzyl)-1H-imidazo[4,5-c]quinolin-4-amine (7) and its niosomal formulation 18 exhibited better activity than Miltefosine. These were then further studied against Leishmania donovani for their ability to arrest the parasites at sub G₀/G₁ phase of cell cycle. The selected TLR7 agonists depicted their ability to arrest higher percentage of parasites in comparison to the standard antileishmanial drugs. Similar observations were seen in case of reactive oxygen species (ROS) generation where parasites treated with the lead TLR7 agonist produced higher ROS than the untreated parasites. These results suggest that TLR7 agonist 7 and its niosomal formulation 18 could be the promising hits for development of a novel drug treating VL. However additional in-vivo studies could aid in their future advancement.