Comparative cytotoxicity of alkyl gallates on mouse tumor cell lines and isolated rat hepatocytes

Frey, Christian; Pavani, Mario; Cordano, G.; Muñoz, Sergio; Rivera, Enrique; Medina, Jorge H.; Morello, Antonio; Maya, Juan Diego; Ferreira, Jorge

doi:10.1016/j.cbpa.2006.03.007

Cited by 33 publications

(25 citation statements)

References 38 publications

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“…The greater resistance of the tumor cell lines could be partly explained by the fact that healthy and cancer cells show differences in their structure and function, such as differences in metabolic activity and molecular composition (Frey et al, 2007) cells could be partly explained by their sensitivity to growth contact inhibition in contrast to 3T6 cells (Todaro and Green, 1963). The contact inhibition property could favor a more differentiated phenotype for the 3T3 cells, in which the cytotoxic effect of the surfactant may be less potent.…”

Section: Discussionmentioning

confidence: 99%

Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Nogueira

Mitjans

Infante

et al. 2011

International Journal of Pharmaceutics

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Surfactants are used as additives in topical pharmaceuticals and drug delivery systems.The biocompatibility of amino acid-based surfactants makes them highly suitable for use in these fields, but tests are needed to evaluate their potential toxicity. Here we addressed the sensitivity of tumor (HeLa, MCF-7) and non-tumor (3T3, 3T6, HaCaT, NCTC 2544) cell lines to the toxic effects of lysine-based surfactants by means of two in vitro endpoints (MTT and NRU). This comparative assay may serve as a new approach for predictive toxicity screening of chemicals prior to pharmaceutical applications. After 24-h of cell exposure to surfactants, differing toxic responses were observed. NCTC 2544 and 3T6 cell lines were the most sensitive, while both tumor cells and 3T3 fibroblasts were more resistant to the cytotoxic effects of surfactants. IC 50 -values revealed that cytotoxicity was detected earlier by MTT assay than by NRU assay, regardless of the compound or cell line. The overall results showed that surfactants with organic counterions were less cytotoxic than those with inorganic counterions. Our findings highlight the relevance of the correct choice and combination of cell lines and bioassays in toxicity studies for a safe and reliable screen of chemicals with potential interest in pharmaceutical industry.

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Section: Discussionmentioning

confidence: 99%

Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Nogueira

Mitjans

Infante

et al. 2011

International Journal of Pharmaceutics

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“…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.…”

Section: The Synthetic N-alkyl Esters Of Gallic Acid (Ga) Also Knownmentioning

confidence: 99%

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

Kratz¹,

Andrighetti-Fröhner²,

Kolling³

et al. 2008

Mem. Inst. Oswaldo Cruz

113

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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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“…3,4) 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. 5,6) Besides the antioxidant activity, other biological activities have been described for this group of molecules, mainly anticancer, [7][8][9][10] antibacterial and antifungal properties. [11][12][13][14][15][16] There are few reports about the antiviral activity of these compounds.…”

mentioning

confidence: 99%

Evaluation of Anti-HSV-2 Activity of Gallic Acid and Pentyl Gallate

Kratz

Andrighetti-Fröhner

Leal

et al. 2008

Biological & Pharmaceutical Bulletin

127

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Herpes simplex virus (HSV) is a DNA-containing enveloped virus that causes common viral infections in humans worldwide leading to a variety of diseases. HSV-1 and HSV-2 can be distinguished on the basis of clinical manifestations (the former is more frequently associated with oral cold sores, while the later causes genital ulcers) and biochemical and serological examinations. In most cases, HSV infection is usually benign or asymptomatic in immunocompetent individuals; however, in patients with an immature or compromised immune system, the infection can be serious and sometimes life-threatening. 1,2) Several nucleoside analogues have been approved for clinical use. Among those, acyclovir is widely used for the systemic treatment of HSV infections. It is a highly selective antiviral agent because it is specifically phosphorylated by viral thymidine kinase in infected cells. However, acyclovir-resistant HSV infection in immunocompromised patients such as transplanted patients and patients with AIDS has recently been observed. Therefore, it is desirable to develop new anti-HSV agents in order to substitute or complement the antiviral drugs available. 3,4)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. 5,6) Besides the antioxidant activity, other biological activities have been described for this group of molecules, mainly anticancer, 7-10) antibacterial and antifungal properties. [11][12][13][14][15][16] There are few reports about the antiviral activity of these compounds. In 1988, the potent inhibition of HSV-1 and HSV-2 by methyl gallate was described. 17) In 2000, as part of the screening of phenolic compounds against HIV-1 integrase, gallic acid was found to be active. 18)More recently, the anti-HSV activity of several gallates was described by our research group, which proposed various structure-activity relationships regarding the antiviral, antioxidant and genotoxic effects.19) Furthermore, the pronounced anti-HSV-1 activity of octyl gallate, and its inhibitory effect against RNA viruses were also recently described. 20,21) In the present study, the anti-HSV-2 activity of gallic acid and pentyl gallate was evaluated followed by the determination of the site of antiviral activity of these compounds. MATERIALS AND METHODSCompounds GA and pentyl gallate (PG) (Fig. 1) were synthesized as previously described.19) The compounds (50 mM) were dissolved in dimethyl sulfoxide, stored at Ϫ20°C protected from light, and further diluted in culture medium prior to use.Cells and Virus African green monkey kidney cells (GMK AH1) were grown in Eagle's minimum essential medium (EMEM, Gibco BRL, Grand Island, NY, U.S.A.) supplemented with 2% fetal calf serum (FSC), 0.05% primaton substance (Kraft Inc., Norwich, CT, U.S.A.), 100 U/ml Göteborg, Sweden. Received November 23, 2007; accepted February 5, 2008; published online February 20, 2008 The synthetic n-alkyl esters of galli...

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Comparative cytotoxicity of alkyl gallates on mouse tumor cell lines and isolated rat hepatocytes

Cited by 33 publications

References 38 publications

Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

Comparative sensitivity of tumor and non-tumor cell lines as a reliable approach for in vitro cytotoxicity screening of lysine-based surfactants with potential pharmaceutical applications

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

Evaluation of Anti-HSV-2 Activity of Gallic Acid and Pentyl Gallate

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