# Silver-N-Heterocyclic Complexes Against Leishmania major: In Vitro, In Vivo and In Silico Therapeutic Activities

## TL;DR

This paper explores new silver-based compounds that may effectively treat cutaneous leishmaniasis, a tropical disease caused by Leishmania parasites.

## Contribution

The study introduces and evaluates two novel silver(I)-N-heterocyclic carbene complexes as potential antileishmanial agents.

## Key findings

- The silver complexes showed therapeutic efficacy against Leishmania promastigotes in vitro and in a mouse model.
- Molecular docking analysis identified complex 2a as having the highest potential antileishmanial activity.

## Abstract

Background/Objectives: Cutaneous leishmaniasis (CL) is a prevalent vector-borne disease characterized by a broad spectrum of clinical manifestations resulting from protozoan parasites belonging to the genus Leishmania. The challenges associated with the treatment of CL are attributable to various factors, including but not limited to: drug resistance, the adverse effects of conventional therapeutic interventions and the imperative for novel therapeutic alternatives to address the global health burden posed by this neglected tropical disease. Methods: In this study, The therapeutic efficacy of two silver(I)-N-heterocyclic carbene (NHC) complexes, namely chloro[1-methallyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2a) and chloro[1-methallyl-3-(4-chlorobenzyl)-5,6-dimethylbenzimidazole-2-ylidene]silver(I) (2b), was evaluated against promastigotes in vitro and in vivo in an experimentally induced CL model in Balb/c mice. Results: The findings of this study indicated that these compounds possess the potential to function as effective therapeutic agents, particularly in the treatment of CL. Subsequently, the silver(I) complexes were analyzed by means of molecular docking against LaGP63, LaARG, N-myristoyltransferase and farnesyl pyrophosphate synthase. Conclusions: According to the docking evaluations, complex 2a emerged as the most notable molecule in terms of its potential antileishmanial activity.