Dicate if changes were made. The Creative Commons Public Domain Dedication
Dicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Zanello et al. Virology Journal (2015) 12:Page 2 ofseverity, to date neither a specific dengue treatment nor an approved vaccine to prevent infection has been developed. Hence, the recognition of dengue signs and the local epidemiological conditions that are associated with medical care are important for reducing the mortality that is associated with the disease [1, 10]. The development of a PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29069523 specific dengue therapy has been challenging. Each structure/protein that is involved in the viral life cycle can serve as a target for the development of novel antiviral agents, and the use of compound libraries appear to be the most effective strategy in searching for active compounds against flaviviruses [11]. Quinic acid (Table 1) is a carboxylated cyclohexanepolyol that is found in several vegetables (potato, carrot, tomato, coffee) and exists either in free form or as esters [12]. It is widely used as an optically-active synthetic precursor in multistep chemical synthesis [13], and it is the starting material that is used for the synthesis of Tamiflu, a drug used in the treatment of influenza A and B [14]. Additionally, quinic acid derivatives are found in propolis produced by Apis mellifera (European honey bee) in the south and southeast regions of Brazil [15]. Furthermore, it has been shown that quinic acid derivatives possess antiviral activities against Human Immunodeficiency Virus (HIV) [16?8], Hepatitis B Virus (HBV) [17, 19], and Herpes Simplex Virus 1 (HSV-1) [20, 21]. In this study, we demonstrated that the amides of quinic acid derivatives present anti-dengue virus activity in vitro in Huh7.5 cells and human PBMCs. Furthermore, we revealed that quinic acid derivatives impair dengue virus replication in Huh7.5 cells.by MTT, which is a tetrazolium salt that is metabolized by cellular reductases only in cells with viable mitochondrial activity [28]. An assessment of Neutral Red (NR) uptake, which demonstrates a cell’s ability to incorporate red dye into lysosomes that maintain physiological pH [29], was performed simultaneously with the MTT assay in the same cell cultures [30]. Based on the results from both assays, it was possible to determine a non-toxic concentration (NTC) of each compound for Huh7.5 as well as the cytotoxic concentration for 50 of the culture (CC50; Table 1). The data show that quinic acid derivatives presented a wide range of cytotoxicity in Huh7.5 cells, with CC50 values varying between 1.56 and >1000 M.Antiviral activityResults and discussionCytotoxicity of quinic acid derivativesBoth quinic acid (Table 1) and several of its derivatives have been shown to protect human lymphocytes from damage induced by X-ray [22] and from cell death induced by tetrahydropapaverolin [23]. Table 1 shows the quinic acid derivatives that were tested in the present study. Recently, it has been demonstrated that the amides of quinic acid derivatives exhibited anti-inflammatory activities both in vitro and in vivo and therefore they may serve as attractive options for therapeutic use [24, 25]. Furthermore, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26437915 one of these amides was found to enhance the survival of C57/Bl6 mice that were exposed to purchase Stattic lethal radiation by 45 [26]. Additionally, a quinic acid ester (QAE) prolonged cell survival by reducing replication in S-phase cell.
