Anti-HSV-1 and anti-HIV-1 activity of gallic acid and pentyl gallate

Abstract

The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by food and pharmaceutical industries. The inhibitory effects of GA and 15 gallates on Herpes Simplex Virus type 1 (HSV-1) and Human Immunodeficiency Virus (HIV-1) replication were investigated here. After a preliminary screening of these compounds, GA and pentyl gallate (PG) seemed to be the most active compounds against HSV-1 replication and their mode of action was characterized through a set of assays, which attempted to localize the step of the viral multiplication cycle where impairment occurred. The detected anti-HSV-1 activity was mediated by the inhibition of virus attachment to and penetration into cells, and by virucidal properties. Furthermore, an anti-HIV-1 activity was also found, to different degrees. In summary, our results suggest that both compounds could be regarded as promising candidates for the development of topical anti-HSV-1 agents, and further studies concerning the anti-HIV-1 activity of this group of molecules are merited.Key words: antiviral -HSV-1 -HIV-1 -gallic acid -pentyl gallate Herpes Simplex Virus type 1 (HSV-1) is an enveloped DNA virus that causes one of the most common viral infections in humans, leading to a variety of diseases ranging from mild to severe and sometimes life-threatening (White & Fenner 1994, Whitley & Rozman 2001. Although several nucleoside analogues have been approved for clinical use, such as acyclovir, immunocompromised patients are at increased risk of severity and recurrent infections, since resistant strains have recently been observed (Brady & Bernstein 2004). Therefore, it is desirable to develop new antiviral agents in order to substitute or complement currently available drugs.The synthetic n-alkyl esters of gallic acid (GA), also known as gallates, especially propyl, octyl and dodecyl gallates, are widely employed as antioxidants by the food and pharmaceutical industries (van der Heijden et al. 1986, Kubo et al. 2002a. Besides the antioxidant activity, other biological activities have been described for this group of molecules, mainly anticancer mechanisms (Fiuza et al. 2004, Kitagawa et al. 2005, Frey et al. 2006, Veluri et al. 2006 as well as antibacterial and antifungal properties (Fujita & Kubo 2002, Kubo et al. 2002b, c, 2003, Stapleton et al. 2004). However, there are few reports about the antiviral activity of these compounds. In 1988, a study described the inhibition of HSV-1 and HSV-2 replication by methyl gallate (Kane et al. 1988). In 2002, as part of the screening of phenolic compounds against HIV-1 integrase, GA was found to be active (Ahn et al. 2002). More recently, several biological activities of a group of gallates were described by our research group, and various structure-activity relationships regarding their anti-HSV-1, antioxidant and genotoxic effects were proposed (Savi et al. 2005). Furthermore, the pronounced anti-HSV-1 activity of octyl gallate, and its inhibitory...

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