2-Phenylaminonaphthoquinones and related compounds: synthesis, trypanocidal and cytotoxic activities.

Abstract

A series of new 2-aminonaphthoquinones and related compounds were synthesized and evaluated in vitro as trypanocidal and cytotoxic agents. Some tested compounds inhibited epimastigote growth and trypomastigote viability. Several compounds showed similar or higher activity and selectivity as compared with current trypanocidal drug, nifurtimox. Compound 4l exhibit higher selectivity than nifurtimox against Trypanosoma cruzi in comparison with Vero cells. Some of the synthesized quinones were tested against cancer cells and normal fibroblasts, showing that certain chemical modifications on the naphthoquinone moiety induce and excellent increase the selectivity index of the cytotoxicity (4g and 10). The results presented here show that the anti-T. cruzi activity of 2-aminonaphthoquinones derivatives can be improved by the replacement of the benzene ring by a pyridine moiety. Interestingly, the presence of a chlorine atom at C-3 and a highly lipophilic alkyl group or aromatic ring are newly observed elements that should lead to the discovery of more selective cytotoxic and trypanocidal compounds.

• Authors: Ivan Sieveking, Pablo Thomas, Juan C Estévez, Natalia Quiñones, Mauricio A Cuéllar, Juan Villena, Christian Espinosa-Bustos, Angélica Fierro, Ricardo A Tapia, Juan D Maya, Rodrigo López-Muñoz, Bruce K Cassels, Ramon J Estévez, Cristian O Salas
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 22 Issue 17 Pg. 4609-20 (Sep 01 2014) ISSN: 1464-3391 [Electronic] England
• PMID: 25127463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Aniline Compounds
• Naphthoquinones
• Trypanocidal Agents

Topics

• Aniline Compounds (chemical synthesis, chemistry, pharmacology)
• Animals
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chlorocebus aethiops
• Dose-Response Relationship, Drug
• Fibroblasts (drug effects)
• Humans
• MCF-7 Cells
• Molecular Structure
• Naphthoquinones (chemical synthesis, chemistry, pharmacology)
• Parasitic Sensitivity Tests
• Structure-Activity Relationship
• Trypanocidal Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• Trypanosoma cruzi (drug effects)
• Vero Cells