# Synthesis and In Vitro Activity of Hypofuran B and Analogs Against Plasmodium Falciparum and Trypanosoma Cruzi

## TL;DR

Researchers synthesized and tested hypofuran B and related compounds for their ability to fight malaria and trypanosomiasis with low toxicity.

## Contribution

The study introduces new hypofuran B analogs with promising antiparasitic activity and low cytotoxicity.

## Key findings

- Hypofuran B analogs showed IC50 values of 5.35–10.35 µg mL−1 against Plasmodium falciparum.
- The most active compounds had CC50 values above 400 µg mL−1, indicating low cytotoxicity.
- Structure–activity relationships were observed, supporting drug-like properties via in silico predictions.

## Abstract

Herein, the synthesis and biological evaluation of hypofuran B and a series of analogs against Trypanosoma cruzi and Plasmodium falciparum is described. The compounds are obtained through crossed aldol condensation between phenylacetaldehyde and furfural derivatives, using reaction conditions optimized according to the aromatic substituents. Yields ranged from 20% to 83%, with E/Z ratios between 89:11 and 98:2. Three compounds are isolated as single crystals suitable for X‐ray diffraction, and their crystal structures are determined. The most active analogs showed IC50 values of 5.35–10.35 µg mL−1 and are further evaluated for cytotoxicity in L929 cells. For P. falciparum, a clear structure–activity–toxicity relationship is observed. The most promising compound displayed a CC50 value above 400 µg mL−1, indicating lower cytotoxicity than chloroquine. In silico predictions also supported favorable drug‐like profiles. Overall, the moderate antiparasitic activity, low cytotoxicity, and consistent structure–activity trends highlight hypofuran B and related drynaran derivatives as promising antimalarial leads.

Hypofuran B, drynaran, and a series of analogs are obtined by crossed aldol condensation from furfural dereivatives. Compunds are tested for in vitro activity agaisnt Trypanosoma cruzi and Plasmodium falciparum. Best results are obtained Against P. falciparum, with IC50 values ranging from 5,35 to 10,35 µg mL−1. A clear structure activity relationship is observed. The most promising compounds showed low cytotoxicity on L929 human cell line (CC50 > 400 µg mL−1) and suitable in silico drug‐like parameters according to the Lipinski's rule of 5.© 2026 WILEY‐VCH GmbH