# Efficient and Rapid Arylation of NH₂‐Unprotected Bromobisindole Ethanamines via Suzuki‐Miyaura Coupling: Generating New Leads Against Leishmania

## TL;DR

Researchers developed a new method to create potent antileishmanial compounds using a chemical reaction called Suzuki-Miyaura coupling.

## Contribution

A rapid and efficient Suzuki-Miyaura coupling method for synthesizing bisindole derivatives with high yields and antileishmanial activity.

## Key findings

- The optimized reaction achieved yields up to 93% for bisindole derivatives.
- Compound 3af showed potent activity against Leishmania infantum with an IC50 of 1.1 µM.
- 3af had a higher selectivity index than the reference drug miltefosine.

## Abstract

Leishmaniasis is a neglected tropical disease which presents significant global health challenges due to the lack of effective vaccines and the limitations of existing chemotherapeutics in view of their toxicity, resistance, and high costs. In this study, we realized a library of novel bisindole derivatives as potential antileishmanial agents through a rapid Suzuki‐Miyaura coupling reaction, utilizing NH2‐unprotected bromobisindole ethanamines and boronic acids. Optimization of reaction conditions allowed for the efficient and selective arylation of these substrates, with yields up to 93%. The compounds were screened for their activity against Leishmania infantum promastigotes. Among the tested bisindole derivatives, 3af (bearing a 4‐vinylphenyl moiety) demonstrated potent antileishmanial activity (IC50 = 1.1 µM) with a higher selectivity index (21.8) compared to the reference drug miltefosine (9.8). A significant activity was also retained against intracellular amastigotes. This study establishes a robust methodology for late‐stage functionalization of bisindoles, also highlighting these derivatives' potential as promising leads for antileishmanial drug development.

A library of novel bisindole derivatives was synthesized through an optimized rapid Suzuki‐Miyaura coupling reaction, utilizing NH2‐unprotected bromobisindole ethanamines and boronic acids with yields up to 93%. The compounds were screened for their activity against L. infantum promastigotes. In particular, bisindole 3af demonstrated potent antileishmanial activity with a higher selectivity index compared to the reference drug miltefosine.