Ivan Malík, Lukáš Stanzel, Jozef Csöllei, Jana Čurillová


In an effort to comprehensively characterize an antioxidant profile of 2-alkoxyphenylcarbamic acid-based compounds containing a 4´-(substituted phenyl)piperazin-1´-yl fragment, they were in vitro screened in the 2,2´-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) derived radical cation (ABTS•+) and ferric reducing antioxidant power (FRAP) assay using the UV/VIS spectrophotometry. The ABTS•+ scavenging (reducing) potential of 1-[3-(2-methoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(4-fluorophenyl)piperazin-1-ium chloride was found to be the most promising and it was comparable to the efficiency of the carvedilol reference drug. Moreover, that 4´-fluoro group-containing compound was regarded as more active than the atenolol standard. When testing the molecules´ power to reduce the ferric 2,4,6-tris (2-pyridyl)-s-triazine complex [Fe(III)(TPTZ)2]3+, the most prospective was 1-[3-(2-ethoxyphenylcarbamoyl)oxy-2-hydroxypropyl]-4-(4-fluorophenyl)piperazin-1-ium chloride. On the other hand, its Fe3+ reducing power was lower compared to both standards carvedilol and atenolol. The study discussed structure–antioxidant properties relationships considering electronic, steric and lipophilic features.


Substituted phenylcarbamates; N-arylpiperazines; antioxidant properties; ABTS•+; FRAP; electronic features; lipophilicity

Full Text:

PDF (1-9)


Antala B., Kyselovicova O., Bacharova L., Tibenska, M. 2008. Changes in QRS amplitude and motor performance in juvenile female athletes during 12 months of intensive training, in Kinesiology Research Trends and Applications, Croatian Academy of Sciences and Arts, Zagreb, Croatia. pp. 145-148.

Benzie IFF., Strain JJ. 1996. The ferric reducing ability of plasma as a measure of ‘antioxidant power’: the FRAP assay. Anal. Biochem. 239: 70-76.

Book WM. 2007. Carvedilol: A nonselective beta blocking agent with antioxidant properties. Congest. Heart Fail. 8: 173-190.

Campos AM., Lissi EA. 1997. Kinetics of the reaction between 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) derived radical cations and phenols. Int. J. Chem. Kinet. 29: 219-224.

Cano A., Hernandez-Ruiz J., Garcia-Canovas F., Acosta M., Arnao MB. 1998. An end-point method for estimation of the total antioxidant activity in plant material. Phytochem. Anal. 9: 196-202.

Caron G., Steyaert G., Pagliara A., Reymond F., Crivori P., et al. 1999. Structure–lipophilicity relationships of neutral and protonated beta-blockers. Part I. Intra- and intermolecular effects in isotropic solvent systems. Helv. Chim. Acta 82: 1211-1222.

Dandona P., Ghanim H., Brooks DP. 2007. Antioxidant activity of carvedilol in cardiovascular disease. J. Hypertens. 25: 731-741.

Eguchi E., Hiroyasu I., Tanabe N., Yatsuya H., Tamakoshi, A. 2014. On behalf of the Japan Collaborative Cohort Study Group. Is the association between healthy lifestyle behaviors and cardiovascular mortality modified by overweight status? The Japan Collaborative Cohort Study. Prev. Med. 62: 142-147.

Feuerstein GZ., Shusterman NH., Ruffolo RR. Jr. 1997. Carvedilol update IV: prevention of oxidative stress, cardiac remodeling and progression of congestive heart failure. Drugs Today. 33: 453-473.

Gillett M., Royle P., Snaith A., Scotland G., Poobalan A., et al. 2012. Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation. Health Technol. Assess. 16: 1-236.

Gomes A., Costa D., Lima JLFC., Fernandes E. 2006. Antioxidant activity of β-blockers: An effect mediated by scavenging reactive oxygen and nitrogen species? Bioorg. Med. Chem. 14: 4568-4577.

Iqbal P., Ahmed D., Asghar MN. 2014. A comparative in vitro antioxidant potential profile of extracts from different parts of Fagonia cretica. Asian Pac. J. Trop. Med. 7: S473-S480.

Katalinic V., Modun D., Music I., Boban M. 2005. Gender differences in antioxidant capacity of rat tissues determined by 2,2´-azinobis (3-ethylbenzothiazoline 6-sulfonate; ABTS) and ferric reducing antioxidant power (FRAP) assays. Comp. Biochem. Physiol. C Toxicol. Pharmacol. 140: 47-52.

Kirsch P. 2004. Modern Fluoroorganic Chemistry. Synthesis, Reactivity, Applications. Wiley-VCh Verlag, Weinheim, Germany, 308 pp.

Kramer JH., Weglicki WB. 1996. A hydroxylated analog of the β-adrenoceptor antagonists, carvedilol, affords exceptional antioxidant protection to postischemic rat hearts. Free Radic. Biol. Med. 21: 813-825.

Kubinyi H. 1993. Methods and principles in medicinal chemistry, in QSAR: Hansch Analysis and Related Approaches, edited by R. Mannhold, P. Krogsgaard-Larsen, H. Timmerman, Wiley-VCh Verlag, Weinheim, Germany, pp. 22-56.

Kyselovičová O., Holienka M., Žamba M., Tibenská M. 2014. Cardiovascular adaptation of juvenile competitive female athletes during the intensive training. PESH (Research in Physical Education, Sport and Health) 3: 75-80.

Loveman E., Frampton GK., Shepherd J., Picot J., Cooper K., et al. 2011. The clinical effectiveness and cost-effectiveness of long-term weight management schemes for adults: a systematic review. Health Technol. Assess. 15: 1-182.

Malík I., Sedlárová E., Csöllei J., Andriamainty F., Kurfürst P., Vančo J. 2006. Synthesis, spectral description, and lipophilicity parameters determination of phenylcarbamic acid derivatives with integrated N-phenylpiperazine moiety in the structure. Chem. Pap. 60: 42-47.

Malík I., Sedlárová E., Csöllei J., Račanská E., Čižmárik J., Kurfürst P. 2004. Synthesis, physico-chemical properties and biological activity of 1 (4-fluorophenyl)-4-[3-(2-, 3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl]piperaziniumchlorides. Sci. Pharm. 72: 283-291.

Malík I., Sedlárová E., Čižmárik J., Andriamainty F., Csöllei, J. 2005. Study of physicochemical properties of 2-, 3-, 4-alkoxyphenylcarbamic acid derivatives with a substituted N-phenylpiperazine moiety in the basic part. Čes. slov. Farm. 54: 235-239.

Mistry B., Keum Y-S., Pandurangan M., Patel RV., Hwan Kim D. 2016. Synthesis of berberine-piperazine conjugates as potential antioxidant and cytotoxic agents. Med. Chem. Res. 25: 2461-2470.

Mistry B., Patel RV., Keum Y-S., Hwan Kim D. 2017. Synthesis of N-Mannich bases of berberine linking piperazine moieties revealing anticancer and antioxidant effects. Saudi J. Biol. Sci. 24: 36-44.

Nichols M., Townsend N., Scarborough P., Rayner M. 2013. Cardiovascular disease in Europe: epidemiological update. Eur. Heart J. 34: 3028-3034.

Re R., Pellegrini N., Proteggente A., Pannala A., Yang M., Rice-Evans CA. 1999. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Rad. Biol. Med. 26: 1231-1237.

Rice-Evans CA., Miller NJ., Paganga G. 1996. Structure–antioxidant activity relationship of flavonoids and phenolic acids. Free Radical Biol. Med. 20: 933-956.

Then M., Szentmihályi K., Sárközi Á., Szöllôsi Varga I. 2003. Examination on antioxidant activity in the greater celandine (Chelidonium majus L.) extracts by FRAP method. Acta Biol. Szeged 47: 115-117.

Tibenská M., Medeková H. 2014. ″Z″-Scores of anthropometric and motor parameters of girls in aerobic gymnastics. Acta Fac. Pharm. Univ. Comen. 61: 55-58.

Townsend N., Nichols M., Scarborough P., Rayner M. 2015. Cardiovascular disease in Europe-epidemiological update 2015. Eur. Heart J. 36: 2696-2705.

Townsend N., Wilson L., Bhatnagar P., Wickramasinghe K., Rayner M., Nichols M. 2016. Cardiovascular disease in Europe: epidemiological update. Eur. Heart J. 37: 3232-3245.

Yue T-L., Cheng HY., Lysko PG., McKenna PJ., et al., 1992. Carvedilol, a new vasodilator and beta adrenoreceptor antagonist, is a antioxidant and free radical scavenger. J. Pharmacol. Exp. Ther. 263: 92-98.



  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Indonesian J Pharm indexed by:


analytics View My Stats