# Exploring Novel Nitrofuryl‐1,3,4‐Thiadiazole‐Based Derivatives: Design, Synthesis, and Evaluation of In Vitro Leishmanicidal and Trypanocidal Activity

## TL;DR

Researchers designed and tested new compounds that show promise in fighting parasitic diseases like leishmaniasis and trypanosomiasis.

## Contribution

A novel compound (18) with submicromolar activity against multiple parasites and good cell selectivity was identified.

## Key findings

- Compound 18 showed submicromolar activity against Leishmania and Trypanosoma species.
- Compound 18 exhibited acceptable selectivity toward THP-1 cells.
- Mechanistic studies indicated a cytostatic effect rather than apoptosis in T. b. brucei cells.

## Abstract

Neglected tropical diseases remain a major global health challenge, highlighting the need for new antiparasitic agents. In this study, a series of substituted 1‐[5‐(5‐nitrofuran‐2‐yl)‐1,3,4‐thiadiazol‐2‐yl]piperidine‐4‐carboxamides was designed, synthesized, and evaluated for in vitro antileishmanial and antitrypanosomal activity. Compound 18 emerged as the most promising derivative, showing submicromolar activity against all tested parasites with acceptable selectivity toward THP‐1 cells. Mechanistic studies in T. b. brucei bloodstream cells revealed a reversible cytostatic effect rather than apoptosis, and assessment of cellular and mitochondrial ROS levels indicated that oxidative stress was not a primary contributor to activity. In silico ADME analysis supported the drug‐likeness of the synthesized compounds. Taken together, these findings identify 18 as a valuable lead for further antiparasitic drug development.

In a series of substituted 1‐[5‐(5‐nitrofuran‐2‐yl)‐1,3,4‐thiadiazol‐2‐yl]piperidine‐4‐carboxamides evaluated for in vitro antileishmanial and antitrypanosomal activity, compound 18 emerged as the most promising derivative, showing submicromolar anti‐parasitic effects targeting diverse Leishmania and Trypanosoma species and acceptable selectivity toward THP‐1 cells.