Virology, Drug Discovery, Applied Microbiology and Biotechnology
3
Scopus Publications
Scopus Publications
The Halogen Effect in [Cu(NHC)X] Compounds: A Case Study on the Anti-Leishmania and Antiviral Activity of [Cu(IPr)X] J. V. Fontes, M. E. F. Agnoli, G. Clauss, M. S. A. Garcia, A. V. P. Ferreira, G. A. Antoniucci, A. L. Costa‐Oliveira, A.C.G. Jardim, D. C. Miguel, C. Abbehausen Chemistryselect, 2025 In this study, we investigated the activity and properties of three neutral Cu(I) N ‐heterocyclic carbene (NHC) complexes—[1,3‐bis(2,6‐diisopropylphenyl) imidazol‐2‐ylidene]copper(I) with Cl, Br, and I, specifically [Cu(IPr)Cl] , [Cu(IPr)Br] , and [Cu(IPr)I] —to evaluate the impact of halogen substitution on anti‐ Leishmania and antiviral activity. The compounds were synthesized using reported methods. 13 C NMR spectroscopy provided insights into the electronic nature of the Cu─X bond by analyzing the NHC C 2 chemical shift. Notably, the iodine derivative exhibited distinct chemical properties compared to its counterparts, displaying a more covalent Cu─I bond. As a result, [Cu(IPr)I] was more susceptible to nucleophilic attack, as confirmed by HOMO–LUMO gap calculations using DFT. Furthermore, this derivative demonstrated the highest lipophilicity and the strongest antioxidant activity in the series, as evidenced by the DPPH assay, surpassing butylated hydroxytoluene (BHT) used as a positive control. Bovine serum albumin (BSA) binding assays indicated weak interaction (10 3 M −1 ) across all compounds, with no significant differences observed. In anti‐ Leishmania assays, [Cu(IPr)I] exhibited the best selectivity index (SI = 4.0), showing greater toxicity to the parasite (EC 50 = 1.5 µM) while being less toxic to the host cell (CC 50 = 6.0 µM). However, this trend did not extend to antiviral studies against the chikungunya virus, where [Cu(IPr)Br] displayed the highest replication inhibition (EC 50 = 0.807 µM) and the best selectivity index (SI = 4.8). Our findings highlight that halogen substitution plays a crucial role in modulating the biological activity of neutral linear metal‐NHC complexes.
Development and validation of Mayaro virus with luciferase reporter genes as a tool for antiviral assays Mikaela dos Santos Marinho, Ya-Nan Zhang, Natasha Marques Cassani, Igor Andrade Santos, Ana Laura Costa Oliveira, Anna Karla dos Santos Pereira, Pedro Paulo Corbi, Bo Zhang, Ana Carolina Gomes Jardim Heliyon, 2024 Arboviruses are etiological agents in an extensive group of emerging diseases with great clinical relevance in Brazil, due to the wide distribution of their vectors and the favorable environmental conditions. Among them, the Mayaro virus (MAYV) has drawn attention since its emergence as the etiologic agent of Mayaro fever, a highly debilitating disease. To study viral replication and identify new drug candidates, traditional antiviral assays based on viral antigens and/or plaque assays have been demonstrating low throughput, making it difficult to carry out larger-scale assays. Therefore, we developed and characterized two DNA-launched infectious clones reporter viruses based on the MAYV strain BeAr 20290 containing the reporter genes of firefly luciferase (FLuc) and nanoluciferase (NLuc), designated as MAYV-firefly and MAYV-nanoluc, respectively. The viruses replicated efficiently with similar properties to the parental wild-type MAYV, and luminescence expression levels reflected viral replication. Reporter genes were also preserved during passage in cell culture, remaining stably expressed for one round of passage for MAYV-firefly and three rounds for MAYV-nanoluc. Employing the infectious clone, we described the effect of Rimantadine, an FDA-approved Alzheimer's drug, as a repurposing agent for MAYV but with a broad-spectrum activity against Zika virus infection. Additionally, we validated MAYV-nanoluc as a tool for antiviral drug screening using the compound EIDD-2749 (4′-Fluorouridine), which acts as an inhibitor of alphavirus RNA-dependent RNA polymerase.
Influence of diimine bidentate ligand in the nitrosyl and nitro terpyridine ruthenium complex on the HSA/DNA interaction and antiviral activity Naiara Cristina Bessas, Evelyn Christine de Souza Arantes, Natasha Marques Cassani, Uriel Enrique Aquino Ruiz, Igor Andrade Santos, Daniel Oliveira Silva Martins, Ana Laura Costa Oliveira, Giovanna André Antoniucci, Arthur Henrique Cavalcante de Oliveira, Gilson DeFreitas-Silva, Ana Carolina Gomes Jardim, Renata Galvão de Lima Nitric Oxide Biology and Chemistry, 2024 Nitric oxide (NO) acts in different physiological processes, such as blood pressure control, antiparasitic activities, neurotransmission, and antitumor action. Among the exogenous NO donors, ruthenium nitrosyl/nitro complexes are potential candidates for prodrugs, due to their physicochemical properties, such as thermal and physiological pH stability. In this work, we proposed the synthesis and physical characterization of the new nitro terpyridine ruthenium (II) complexes of the type [RuII(L)(NO2)(tpy)]PF6 where tpy = 2,2':6′,2″-terpyridine; L = 3,4-diaminobenzoic acid (bdq) or o-phenylenediamine (bd) and evaluation of influence of diimine bidentate ligand NH.NHq-R (R = H or COOH) in the HSA/DNA interaction as well as antiviral activity. The interactions between HSA and new nitro complexes [RuII(L)(NO2)(tpy)]+ were evaluated. The Ka values for the HSA–[RuII(bdq)(NO2)(tpy)]+ is 10 times bigger than HSA–[RuII(bd)(NO2)(tpy)]+. The sites of interaction between HSA and the complexes via synchronous fluorescence suppression indicate that the [RuII(bdq)(NO2)(tpy)]+ is found close to the Trp-241 residue, while the [RuII(bd)(NO2)(tpy)]+ complex is close to Tyr residues. The interaction with fish sperm fs-DNA using direct spectrophotometric titration (Kb) and ethidium bromide replacement (KSV and Kapp) showed weak interaction in the system fs-DNA-[RuII(bdq)(NO)(tpy)]+. Furthermore, fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+ system showed higher intercalation constant. Circular dichroism spectra for fs-DNA–[RuII(bd)(NO2)(tpy)]+ and fs-DNA–[RuII(bd)(NO)(tpy)]3+, suggest semi-intercalative accompanied by major groove binding interaction modes. The [RuII(bd)(NO2)(tpy)]+ and [RuII(bd)(NO)(tpy)]3+ inhibit replication of Zika and Chikungunya viruses based in the nitric oxide release under S-nitrosylation reaction with cysteine viral.
