Antileishmanial and Anti-Chikungunya Activity of Cu(I)-N-Heterocyclic Carbenes

Author(s)

Fontes, Josielle, V ; Santos, Igor A. ; Rosa, Leticia B. ; Lima, Rochanna L. A. ; Jardim, Ana C. G. ; Miguel, Danilo C. ; Abbehausen, Camilla

• Document type: Journal article
• Source: CHEMISTRYSELECT; v. 7, n. 31, p. 10-pg., 2022-08-19.

Abstract

Neglected tropical diseases such as Leishmaniasis and Chikungunya fever are worldwide public health challenges mainly affecting tropical and subtropical countries. One cationic [Cu-(1)(NHC)(2)](+) (4) and two neutral [Cu(I)(NHC)CI] complexes, where NHC=1,3-bis(mesityl)imidazole-2-ylidene (IMes) (5) or 1,3-bis-(2,6-diisopropylphenyl)imidazole-2-ylidene (IPr) (6), had their in vitro activity evaluated towards Leishmonia ornozonensis and Chikungunya virus (CHIKV). The compound (6) inhibited 95% of L. omozonensis infection in RAW macrophages at 10 mu M and 90% of the CHIKV replication at 2 mu M in BHK-21 cells. Otherwise, the other compounds showed higher cytotoxicity in BHK-21 and RAW or lower antiparasitic or antiviral activities. The best activity of compound 6 can be explained by slower ligand exchange with solvent molecules measured by H-1 NMR technique and the best hydrophilic/lipophilic balance (log P= -0.684 +/- 0.055) in the series determined by shake flask method. Antioxidant activity measured by reduction of DPPH revealed a moderate redox ability of all complexes. The binding constant of (6) with bovine serum albumin (BSA) represents the weakest in the series (10(3)). The chemical and in vitro evaluation reported here represent a novel application and chemical insights for the design of [Cu(I)(NHC)L] metallodrugs for these infectious diseases. (AU)

• FAPESP's process: 19/16904-2 - Targeted metallodrug design for antileishmaniasis
• Grantee: Camilla Abbehausen
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/21129-4 - The role of fatty acid-binding proteins in the macrophage infection by Leishmania: a potential target for new drugs against leishmaniasis
• Grantee: Danilo Ciccone Miguel
• Support Opportunities: Research Grants - Young Investigators Grants