The effect of benzophenone on HIV-1 infection

Benzophenones represent a potentially useful alternative to the current chemotherapeutic strategies to treat and/or prevent infectious diseases.Objective: This in vitro study evaluated the toxicity and the anti-HIV-1 activity of 7-epiclusianone. Methods: The benzophenone 7-epiclusianone was isolated from a hexane extract of Rheedia gardeniana fruit pericarp. The purity level was >98% as determined by HPLC. Toxicity was evaluated using flurometric quantification of cellular viability.The anti-HIV activity on TZM cells, HeLa cells expressing CD4 and both HIV-1 co-receptors CXCR4 and CCR5, was determined using a luciferase reporter. To elucidate the molecular mechanisms of action of these agents we isolated the total RNA from TZM cells and performed Illumina whole genome expression profiling and Pathway-focused qRT-PCR array. The data management, enrichment analysis and pathway analysis were determined with MetaCore software (Thomson Reuters). Results: 7-epiclusianone was toxic above 25µM. The anti-HIV activity was dose-dependent and inhibited 50% of HIV infection at 1.5µM. The expression of both CCR5 and CD4 receptors for HIV were downregulated by benzophenone. Conclusion: 7-epiclusianone is a promising naturally occurring agent displaying anti-HIV activity. The putative pathway by which 7-epiclusianone affect HIV-1 infection may involve the downregulation of chemokine receptor.