Evaluation of Antiviral Activity of Cyclic Ketones against Mayaro Virus.

Mayaro virus (MAYV) is a neglected arthropod-borne virus found in the Americas. MAYV infection results in Mayaro fever, a non-lethal debilitating disease characterized by a strong inflammatory response affecting the joints and muscles. MAYV was once considered endemic to forested areas in Brazil but has managed to adapt and spread to urban regions using new vectors, such as Aedes aegypti, and has the potential to cause serious epidemics in the future. Currently, there are no vaccines or specific treatments against MAYV. In this study, the antiviral activity of a series of synthetic cyclic ketones were evaluated for the first time against MAYV. Twenty-four compounds were screened in a cell viability assay, and eight were selected for further evaluation. Effective concentration (EC50) and selectivity index (SI) were calculated and compound 9-(5-(4-chlorophenyl]furan-2-yl)-3,6-dimethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2))-dione (9) (EC50 = 21.5 µmol·L-1, SI = 15.8) was selected for mechanism of action assays. The substance was able to reduce viral activity by approximately 70% in both pre-treatment and post-treatment assays.

In vitro tripanocidal effect of 1,8-dioxooctahydroxanthenes (xanthenodiones) and tetraketones and improvement of cardiac parameters in vivo.

OBJECTIVE: Trypanosoma cruzi infection affects millions of people worldwide, and the drugs available for its treatment have limited efficacy. 1,8-Dioxooctahydroxanthenes and tetraketones are compounds with important biological applications. The aim of this study was to assess the trypanocidal and inflammatory activities of nine 1,8-dioxooctahydroxanthenes (1-9) and three tetraketones (10-12). METHODS AND RESULTS: By in vitro killing assay, three compounds were able to eliminate CL TdTomato expressing strain of T. cruzi, 9 (IC50=30.65µM), 10 (IC50=14.11µM), and 11 (IC50=26.43µM). However, only 9 was not toxic to Vero cells. Next, to evaluate the in vivo antitrypanosomal and immunological efficacy of 9, Swiss mice were infected with the Y and CL strains of T. cruzi and treated for 10 days with 50mg/kg of 9. This compound reduced the cardiac inflammatory infiltration in animals infected with both strains. Rank's ligand (RankL), CCL2, and interferon (IFN)-γ were measured in the cardiac tissue homogenate of the Y-strain-infected animals, and no interference of 9 was observed. However, compound 9 increased the RankL and interleukin (IL)-10 levels in CL-infected mice. No hepatic and renal toxicity was observed. CONCLUSION: Our findings showed that 1,8-dioxooctahydroxanthene has antiparasitic effect and ameliorates the cardiac inflammatory parameters related to T. cruzi infection.

Xanthenedione (and intermediates involved in their synthesis) inhibit Zika virus migration to the central nervous system in murine neonatal models.

Zika Virus (ZIKV), an arbovirus that belongs to the Flaviviridae family, has become a global concern since its outbreak in the Americas in 2015. With symptoms similar to other Flavivirus as Dengue and Yellow Fever viruses, infections by ZIKV have also been related to several neurological complications such as microcephaly in newborns and Guillain-Barre syndrome. Considering the high prevalence of ZIKV infection in certain areas, the risks that the virus poses to fetal brain development, and the fact that there is no vaccine or specific prophylaxis available, an effective treatment capable of preventing the infection is of potential interest. Therefore, in the present investigation, the antiviral activity on ZIKV of a group of xanthenodiones and intermediate ketones involved in their synthesis was evaluated for the first time. It was found that the compound 2-(2,6-dichlorobenzylidene)cyclohexane-1,3-dione 27 was able to completely inhibit the viral infection of Vero cells as well as to significantly reduce viral load in the brains of newborn Swiss mice. These effects are related to a direct interaction of the compound with the viral particle, blocking the viral adsorption.