title: Evaluation of anti-herpetic and antioxidant activities, and cytotoxic and genotoxic effects of synthetic alkyl-esters of gallic acid.
abstract: The n-alkyl esters of gallic acid (CAS 13857-8) have a diverse range of uses as antioxidants in food, cosmetics and pharmaceutical industries. Pharmaceutical studies performed with these compounds have found that they have many therapeutic potentialities including anti-cancer, antiviral and antimicrobial properties. However, more interest has been devoted to their antioxidant activity due to the ability to scavenge and reduce reactive oxygen species (ROS) formation. In this study, gallic acid and 14 different alkyl gallates were tested. The cytotoxicity and anti-herpetic (HSV-1, KOS and 29-R strains) activity were studied by using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) colorimetric assay and the cell viability by using the Trypan blue dye exclusion method. The genotoxicity was studied by the Comet assay and the antioxidant activity by using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging and microsomal lipid peroxidation-inhibiting activities. The results showed that all the tested compounds have anti-herpetic activity at non cytotoxic concentrations with selectivity indices (SI = CC50/EC50) varying from 0.89 to 18.34, depending on the used HSV-1 strain. It was observed that all tested alkyl gallates showed some degree of genotoxicity, at the tested concentrations, except cetyl gallate, at 256.60 micromol/L (p <0.05, t-Student test), probably induced by ROS released by infected cells and/or by the alkyl gallates that were not antioxidants, at the tested concentrations, in which they demonstrated anti-herpetic activity. The hydroxyl groups can induce DNA damage due interactions with some metal ions, which are naturally present in the culture medium supplemented with fetal bovine serum, probably explaining the genotoxicity detected. However, the obtained results showed considerable antioxidant activity at smaller concentrations, when compared to quercetin which is considered as a reference drug due to its already described antioxidant potential: DPPH radical scavenging activity with IC50 values varying from 17 to 31 micromol/L; and microsomal lipid peroxidation-inhibiting activity with IC50 values varying from 21 to 59 micromol/L. It was observed that the presence of hydroxyl groups in these molecules is important for their pharmacological profile, but the length of the lateral carbonic chain does not have considerable influence.
authors.affiliation: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina (UFSC), Florianópolis, SC (Brazil).
authors.forename: Luciane A
authors.initials: LA
authors.lastname: Savi
authors.forename: Paulo C
authors.initials: PC
authors.lastname: Leal
authors.forename: Tiago O
authors.initials: TO
authors.lastname: Vieira
authors.forename: Rober
authors.initials: R
authors.lastname: Rosso
authors.forename: Ricardo J
authors.initials: RJ
authors.lastname: Nunes
authors.forename: Rosendo A
authors.initials: RA
authors.lastname: Yunes
authors.forename: Tânia B
authors.initials: TB
authors.lastname: Creczynski-Pasa
authors.forename: Célia R M
authors.initials: CR
authors.lastname: Barardi
authors.forename: Cláudia M O
authors.initials: CM
authors.lastname: Simões
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000378:metabolism; D001713:Biphenyl Compounds; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D020552:Comet Assay; D016166:Free Radical Scavengers; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D006564:Herpesviridae / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000138:chemical synthesis / Q000633:toxicity*; D010851:Picrates / Q000737:chemistry; D012996:Solutions; D014709:Vero Cells
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D000998:Antiviral Agents; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D007202:Indicators and Reagents; D009153:Mutagens; D010851:Picrates; D012996:Solutions; D005707:Gallic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D001205:Ascorbic Acid