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Synthesis, Characterization and In Vitro Antioxidant Activities of New Benzimidazole Ruthenium- (II) Complexes

Year 2017, , 738 - 747, 08.12.2017

Serap Şahin Bölükbaşı , Neslihan Şahin

https://doi.org/10.17776/csj.349326

Abstract

In
this study; it was first intended to synthesize 1-substituted benzimidazole
ligands containing a nitrogen-bound bulky or functional group and then
preparing Ru- (II) -N coordinated metal complexes of these ligands. At last
stage of study it has been investigated that the antioxidant activities of
synthesized metal-complexes. Inert atmosphere-vacuum system has been used for the synthesis of all
complexes. Their structure were characterized by spectroscopic techniques. The in
vitro antioxidant activities of metal complexes were investigated based on the
scavenging of hydroxyl, superoxide and 2,2-diphenyl-1-picrylhydrazyl (DPPH)
radicals. In addition, total antioxidant activity of each metal-complex was
also determined. It was determined that total antioxidant activities
of metal-complexes increased by the order of 
3, 4 and 2. Because of decreasing IC50 values indicates that
increasing antioxidant activity, DPPH radical scavenging activity of complex 2, which has lower IC50 value,
was greater than complex 4. IC50
values have not seen for complex 3
for DPPH. It was observed that hydroxyl radical scavenging activities of
complexes increased 4, 3 and 2, while superoxide
radical scavenging activities of complexes increased by the order of 3,
2 and 4, respectively.  As a result; newly
synthesized Ru (II) -azole complexes have been found to have significant
antioxidant activity against DPPH, hydroxyl and superoxide radicals.

Keywords

Benzimidazole Ruthenium DPPH Hydroxyl Radical Superoxide Radical

References

  • [1]. Gülçin I., Oktay M., Küfrevioglu, Ö.I., Aslan A. Determination of antioxidant activity of lichen Cetraria islandica [L] Ach. J Ethnopharmacol. 2002, 79, 325-329.
  • [2]. Halliwell B., Gutteridge J.M.C. Free Radicals in Biology and Medicine. Clarendon Press: Oxford. 1989, p. 23-30
  • [3]. Halliwell B. Free Radicals, Antioxidants, and Human Disease: Curiosity, Cause, or Consequence? Lancet. 1994, 344, 721-724.
  • [4]. Cerutti P. Oxy-Radical and Cancer: Lancet. 1994, 344, 862-863.
  • [5]. Dean R.T., Gieseg S., Davies M.J. Reactive species and their accumulation on radical-damaged proteins. Trends Biochem Sci. 1993, 18, 437-441.
  • [6]. Diplock A.T., Rice-Evans C.A., Burdon R.H. Is There a Significant Role for Lipid Peroxidation in The Causation of Malignancy and for Antioxidants in Cancer Prevention? Cancer Res. 1994, 54, 1952-1956.
  • [7]. Parejo I., Viladomat F., Bastida J., Rosas-Romero A., Flerlage N., Burillo J., Codina C., Comparison between the radical scavenging activity and antioxidant activity of six distilled and nondistilled mediterranean herbs and aromatic plants. J Agric Food Chem. 2002, 50, 6882-6890.
  • [8]. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007, 19(9), 1807-1819.
  • [9]. Bagchi D., Bagchi M., Stohs S.J., Das D.K., Ray S.D., Kuszynski C.A., Joshi S.S, Pruess H.G. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 2000, 148, 187-197.
  • [10]. Datta K., Sinha S. Chattopadhyay P. Reactive oxygen species in health and disease. Natl Med J India. 2000, 13, 304-10.
  • [11]. Nagar R. Syntheses, characterization, and microbial activity of some transition metal complexes involving potentially active O and N donor heterocyclic ligands. J Inorg Biochem. 1990, 40, 349-356.
  • [12]. Cavigiolioa G., Benedettoa L., Boccaleria E., Colangelob D., Vianob I., Osellac D. Pt[II] complexes with different N-donor aromatic ligands for specific inhibition of telmerase. Inorg Chim Acta. 2000, 305, 61-68.
  • [13]. Klimesova V.K., Koci J., Waisser K., Kaustová J. New benzimidazole derivatives as antimycobacterial agents. Farmaco. 2002, 57, 259-265.
  • [14]. He Y., Wu B., Yang J., Robinson D., Risen L., Ranken R., Blyn L., Sheng S., Swayze E.E. 2-Piperidin-4-yl-benzimidazoles with broad spectrum antibacterial activities. Bioorg Med Chem Lett. 2003, 13, 3253-3256.
  • [15]. Ayhan G., Altanlar N. Synthesis and antimicrobial activities of some new benzimidazole derivatives Farmaco. 2003, 58, 1345-1350.
  • [16]. Ganeshpandian M., Loganathan R., Suresh E., Riyasdeen A., Akbarsha M.A., Palaniandavar M. New ruthenium[II] arene complexes of anthracenyl-appended diazacycloalkanes: effect of ligand intercalation and hydrophobicity on DNA and protein binding and cleavage and cytotoxicity. Dalton Trans. 2014, 43, 1203-1219.
  • [17]. Jiang G.B., Xie Y.Y., Lin G.J., Huang H.L., Liang Z.H., Liu Y.J. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium[II] polypyridyl complexes. J Photochem Photobiol. B 2013, 129, 48-56
  • [18]. Anitha P., Chitrapriya N., Jang Y.J., Viswanathamurthi P. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity of new ruthenium[II] complexes of thiosemicarbazone/semicarbazone bearing 9,10-phenanthrenequinone. J Photochem Photobiol B. 2013, 129, 17-26.
  • [19]. Krstić M., Sovilj S.P., Grgurić-Šipka S., Evans I.R., Borozan S., Santibanez J.F. Synthesis, structural and spectroscopic characterization,in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido[p-cymene] complexes of ruthenium[II] containing N-alkylphenothiazines. Eur J Med Chem. 2011, 46, 4168-4177.
  • [20]. Öztürk S., Akkurt M., Küçükbay H., Fun H.K. Crystal structure of 1-[2-Ethoxyethyl]-3-[2-methoxyethyl]-benzimidazolium chloride-monohydrrate, [C14H21N2O2]+.Cl-.H2O. Anal Sci. 2001, 17, 1015-1016.
  • [21]. Üstün E., Koç Ş., Demir S., Özdemir İ. Carbon monoxide-releasing properties and DFT/TDDFT analiysis of [Mn[CO]3[bpy]L]PF6 type novel manganese complexes. J Organomet Chem. 2016, 815-816, 16-22.
  • [22]. Özdemir İ., Şahin N., Gök Y., Demir S., Çetinkaya B. İn situ generated 1-alkylbenzimidazole-palladium catalyst for the Suzuki coupling of aryl chlorides. J Mol Catal A Chem. 2005, 234, 181-185.
  • [23]. Cuendet M., Hostettmann K., Potterat O.H. Iridoid Glucosides with Free Radical Scavenging Properties from Fagraea blumei. Helv Chim Acta. 1997, 80, 1144-1152.
  • [24]. Kunchandy E., Rao M.N.A. Oxygen Radical Scavenching Activity of Curcumin. Int J Pharm. 1990, 58, 237-240
  • [25]. Ohkawa H., Ohishi N., Yagi K. Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction. Anal Biochem. 1979, 95, 351-358.
  • [26]. Imanari T., Hirota M., Miyazaki M., Hayakawa K., Tamura Z. Improved assay method for superoxide dismutase. Igaku No Ayumi. 1977, 101, 496-497.
  • [27]. Prieto P., Pineda M., Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem. 1999, 269, 337-341.
  • [28]. Edwin N.F., Huang S.W., Kanner J. Bruce German, J. Interfacial phenomena in the evaluation of antioxidants: bulk oils versus emulsions. J Agric Food Chem. 1994, 42, 1054-1059.
  • [29]. Kolevai I.I, van Beek T.A., Linssen J.P., de Groot A., Evstatieva L.N. Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochem Anal. 2002, 13, 8-17.
  • [30]. Kulisic T., Radonic A., Katalinic V., Milos M. Use of different methods for testing antioxidative activity of oregano essential oil. Food Chem. 2004, 85, 633-640.
  • [31]. Macdonald-Wicks L.K., Wood L.G., Garg M.L. Methodology For The Determination Of Biological Antioxidant Capacity İn Vitro: A Review. J Sci Food Agric. 2006, 86, 2046-2056.
  • [32]. Scalzo R.L. Organic Acids İnfluence on DPPH Scavenging By Ascorbic Acid. Food Chem. 2008, 107, 40-43.
  • [33]. Menteşe E., Yılmaz F., Baltaş N., Bekircan O., Kahveci B. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings. J Enzyme Inhib Med Chem. 2015, 30, 435-441
  • [34]. Menteşe E., Ülker S., Kahveci B. Synthesis and Study Of Α-Glucosıdase Inhıbıtory, Antımıcrobıal And Antıoxıdant Actıvıtıes Of Some Benzımıdazole Derıvatıves Contaınıng Trıazole, Thıadıazole, Oxadıazole, And Morpholıne Rıngs. Chem Heterocycl Compd 2015, 50, 1671-1682.
  • [35]. Liu Y.J., Zeng C.H., Liang Z.H., Yao J.H., Huang H.L., Li Z.Z., Wu F.H. Synthesis of ruthenium[II] complexes and characterization of their cytotoxity i,n vitro, apoptosis, DNA-binding and antioxidant activity. Eur J Med Chem. 2010, 45, 3087-3095.
  • [36]. Xian-Lan H., Zhen-Hua L., Mao-Hua Z., Ruthenium[II] complexes: structure, DNA binding, photocleavage, antioxidant activity, and theoretical studies. J Coord Chem. 2011, 64, 3792-807.
  • [37]. Hong-Liang H., L. Zheng-Zheng, L. Zhen-Hua, J.H. Yao, Y.J. Liu, Synthesis, cellular uptake, apopotosis, cytotoxicity, cell cycle arrest, interaction with DNA and antioxidant activity of ruthenium[II] complexes. Eur J Med Chem. 2011, 46, 3282-3290
  • [38]. Wood J.E., Senthılmohan S.T., Peskın A.V. Antioxidant Activity of Procyanidin-Containing Plant Extract at Different Phs. Food Chem. 2002, 77, 155-161.
  • [39]. Kılcıgil G.A., Kuş C., Özdamar E. D., Eke B.C., İşcan M. Synthesis and Antioxidant Capacities of Some New Benzimidazole Derivatives. Arch Pharm [Weinheim] 2007, 340, 607-611.

Yeni Benzimidazol Rutenyum-(II) Komplekslerinin Sentezi, Karakterizasyonu ve İn Vitro Antioksidan Aktiviteleri

Year 2017, , 738 - 747, 08.12.2017

Serap Şahin Bölükbaşı , Neslihan Şahin

https://doi.org/10.17776/csj.349326

Abstract

Bu
çalışmada; ilk olarak azota bağlı hacimli veya fonksiyonel grup içeren
1-sübstitüye benzimidazol ligantlarının sentezlenmesi
ve daha sonra sentezlenen bu ligantların Ru-(II)-N-koordine metal
komplekslerinin  hazırlanması
amaçlanmıştır. Son
aşamada ise sentezlenen metal-komplekslerin antioksidan aktiviteleri çalışılmıştır. Bileşeklerin sentezlenmesinde inert atmosfer-vakum
sistemi kullanılmıştır. Tüm komplekslerin 
yapıları spektroskopik tekniklerle aydınlatılmıştır. Sentezlenen metal
komplekslerin in vitro antioksidan
aktiviteleri; hidroksil, süperoksit ve DPPH radikallerini süpürme özellikleri
ile araştırılmıştır. Ayrıca her bir metal-kompleksin toplam antioksidan
aktivitesi de saptanmıştır. Metal-komplekslerin toplam antioksidan aktivitelerinin 3, 4 ve 2 sıralamasıyla arttığı saptanmıştır. Azalan IC50 değeri
artan antioksidan aktiviteye işaret ettiğinden, daha düşük IC50 değerine
sahip olan 2 numaralı bileşiğin DPPH
radikali süpürme aktivitesinin 4
numaralı bileşikten daha yüksek olduğu bulunmuştur. DPPH radikali süpürme
aktivitesinde, 3 numaralı bileşik
için IC50 değeri gözlenmemiştir. Bileşiklerin hidroksil radikali
süpürme aktivitelerinin 4, 3 ve 2 sıralamasıyla artarken, süperoksit
radikali süpürme aktivitelerinin ise; 3,
2 ve 4 sıralamasıyla arttığı
bulunmuştur. Sonuç olarak; yeni
sentezlenen Ru(II)-azol komplekslerinin DPPH, hidroksil ve süperoksit
radikallerine karşı önemli antioksidan aktiviteye sahip oldukları bulunmuştur.

Keywords

Benzimidazol Rutenyum DPPH Hidroksil Radikali Süperoksit Radikali

References

  • [1]. Gülçin I., Oktay M., Küfrevioglu, Ö.I., Aslan A. Determination of antioxidant activity of lichen Cetraria islandica [L] Ach. J Ethnopharmacol. 2002, 79, 325-329.
  • [2]. Halliwell B., Gutteridge J.M.C. Free Radicals in Biology and Medicine. Clarendon Press: Oxford. 1989, p. 23-30
  • [3]. Halliwell B. Free Radicals, Antioxidants, and Human Disease: Curiosity, Cause, or Consequence? Lancet. 1994, 344, 721-724.
  • [4]. Cerutti P. Oxy-Radical and Cancer: Lancet. 1994, 344, 862-863.
  • [5]. Dean R.T., Gieseg S., Davies M.J. Reactive species and their accumulation on radical-damaged proteins. Trends Biochem Sci. 1993, 18, 437-441.
  • [6]. Diplock A.T., Rice-Evans C.A., Burdon R.H. Is There a Significant Role for Lipid Peroxidation in The Causation of Malignancy and for Antioxidants in Cancer Prevention? Cancer Res. 1994, 54, 1952-1956.
  • [7]. Parejo I., Viladomat F., Bastida J., Rosas-Romero A., Flerlage N., Burillo J., Codina C., Comparison between the radical scavenging activity and antioxidant activity of six distilled and nondistilled mediterranean herbs and aromatic plants. J Agric Food Chem. 2002, 50, 6882-6890.
  • [8]. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007, 19(9), 1807-1819.
  • [9]. Bagchi D., Bagchi M., Stohs S.J., Das D.K., Ray S.D., Kuszynski C.A., Joshi S.S, Pruess H.G. Free radicals and grape seed proanthocyanidin extract: Importance in human health and disease prevention. Toxicology. 2000, 148, 187-197.
  • [10]. Datta K., Sinha S. Chattopadhyay P. Reactive oxygen species in health and disease. Natl Med J India. 2000, 13, 304-10.
  • [11]. Nagar R. Syntheses, characterization, and microbial activity of some transition metal complexes involving potentially active O and N donor heterocyclic ligands. J Inorg Biochem. 1990, 40, 349-356.
  • [12]. Cavigiolioa G., Benedettoa L., Boccaleria E., Colangelob D., Vianob I., Osellac D. Pt[II] complexes with different N-donor aromatic ligands for specific inhibition of telmerase. Inorg Chim Acta. 2000, 305, 61-68.
  • [13]. Klimesova V.K., Koci J., Waisser K., Kaustová J. New benzimidazole derivatives as antimycobacterial agents. Farmaco. 2002, 57, 259-265.
  • [14]. He Y., Wu B., Yang J., Robinson D., Risen L., Ranken R., Blyn L., Sheng S., Swayze E.E. 2-Piperidin-4-yl-benzimidazoles with broad spectrum antibacterial activities. Bioorg Med Chem Lett. 2003, 13, 3253-3256.
  • [15]. Ayhan G., Altanlar N. Synthesis and antimicrobial activities of some new benzimidazole derivatives Farmaco. 2003, 58, 1345-1350.
  • [16]. Ganeshpandian M., Loganathan R., Suresh E., Riyasdeen A., Akbarsha M.A., Palaniandavar M. New ruthenium[II] arene complexes of anthracenyl-appended diazacycloalkanes: effect of ligand intercalation and hydrophobicity on DNA and protein binding and cleavage and cytotoxicity. Dalton Trans. 2014, 43, 1203-1219.
  • [17]. Jiang G.B., Xie Y.Y., Lin G.J., Huang H.L., Liang Z.H., Liu Y.J. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity studies of ruthenium[II] polypyridyl complexes. J Photochem Photobiol. B 2013, 129, 48-56
  • [18]. Anitha P., Chitrapriya N., Jang Y.J., Viswanathamurthi P. Synthesis, characterization, DNA interaction, antioxidant and anticancer activity of new ruthenium[II] complexes of thiosemicarbazone/semicarbazone bearing 9,10-phenanthrenequinone. J Photochem Photobiol B. 2013, 129, 17-26.
  • [19]. Krstić M., Sovilj S.P., Grgurić-Šipka S., Evans I.R., Borozan S., Santibanez J.F. Synthesis, structural and spectroscopic characterization,in vitro cytotoxicity and in vivo activity as free radical scavengers of chlorido[p-cymene] complexes of ruthenium[II] containing N-alkylphenothiazines. Eur J Med Chem. 2011, 46, 4168-4177.
  • [20]. Öztürk S., Akkurt M., Küçükbay H., Fun H.K. Crystal structure of 1-[2-Ethoxyethyl]-3-[2-methoxyethyl]-benzimidazolium chloride-monohydrrate, [C14H21N2O2]+.Cl-.H2O. Anal Sci. 2001, 17, 1015-1016.
  • [21]. Üstün E., Koç Ş., Demir S., Özdemir İ. Carbon monoxide-releasing properties and DFT/TDDFT analiysis of [Mn[CO]3[bpy]L]PF6 type novel manganese complexes. J Organomet Chem. 2016, 815-816, 16-22.
  • [22]. Özdemir İ., Şahin N., Gök Y., Demir S., Çetinkaya B. İn situ generated 1-alkylbenzimidazole-palladium catalyst for the Suzuki coupling of aryl chlorides. J Mol Catal A Chem. 2005, 234, 181-185.
  • [23]. Cuendet M., Hostettmann K., Potterat O.H. Iridoid Glucosides with Free Radical Scavenging Properties from Fagraea blumei. Helv Chim Acta. 1997, 80, 1144-1152.
  • [24]. Kunchandy E., Rao M.N.A. Oxygen Radical Scavenching Activity of Curcumin. Int J Pharm. 1990, 58, 237-240
  • [25]. Ohkawa H., Ohishi N., Yagi K. Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction. Anal Biochem. 1979, 95, 351-358.
  • [26]. Imanari T., Hirota M., Miyazaki M., Hayakawa K., Tamura Z. Improved assay method for superoxide dismutase. Igaku No Ayumi. 1977, 101, 496-497.
  • [27]. Prieto P., Pineda M., Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem. 1999, 269, 337-341.
  • [28]. Edwin N.F., Huang S.W., Kanner J. Bruce German, J. Interfacial phenomena in the evaluation of antioxidants: bulk oils versus emulsions. J Agric Food Chem. 1994, 42, 1054-1059.
  • [29]. Kolevai I.I, van Beek T.A., Linssen J.P., de Groot A., Evstatieva L.N. Screening of plant extracts for antioxidant activity: a comparative study on three testing methods. Phytochem Anal. 2002, 13, 8-17.
  • [30]. Kulisic T., Radonic A., Katalinic V., Milos M. Use of different methods for testing antioxidative activity of oregano essential oil. Food Chem. 2004, 85, 633-640.
  • [31]. Macdonald-Wicks L.K., Wood L.G., Garg M.L. Methodology For The Determination Of Biological Antioxidant Capacity İn Vitro: A Review. J Sci Food Agric. 2006, 86, 2046-2056.
  • [32]. Scalzo R.L. Organic Acids İnfluence on DPPH Scavenging By Ascorbic Acid. Food Chem. 2008, 107, 40-43.
  • [33]. Menteşe E., Yılmaz F., Baltaş N., Bekircan O., Kahveci B. Synthesis and antioxidant activities of some new triheterocyclic compounds containing benzimidazole, thiophene, and 1,2,4-triazole rings. J Enzyme Inhib Med Chem. 2015, 30, 435-441
  • [34]. Menteşe E., Ülker S., Kahveci B. Synthesis and Study Of Α-Glucosıdase Inhıbıtory, Antımıcrobıal And Antıoxıdant Actıvıtıes Of Some Benzımıdazole Derıvatıves Contaınıng Trıazole, Thıadıazole, Oxadıazole, And Morpholıne Rıngs. Chem Heterocycl Compd 2015, 50, 1671-1682.
  • [35]. Liu Y.J., Zeng C.H., Liang Z.H., Yao J.H., Huang H.L., Li Z.Z., Wu F.H. Synthesis of ruthenium[II] complexes and characterization of their cytotoxity i,n vitro, apoptosis, DNA-binding and antioxidant activity. Eur J Med Chem. 2010, 45, 3087-3095.
  • [36]. Xian-Lan H., Zhen-Hua L., Mao-Hua Z., Ruthenium[II] complexes: structure, DNA binding, photocleavage, antioxidant activity, and theoretical studies. J Coord Chem. 2011, 64, 3792-807.
  • [37]. Hong-Liang H., L. Zheng-Zheng, L. Zhen-Hua, J.H. Yao, Y.J. Liu, Synthesis, cellular uptake, apopotosis, cytotoxicity, cell cycle arrest, interaction with DNA and antioxidant activity of ruthenium[II] complexes. Eur J Med Chem. 2011, 46, 3282-3290
  • [38]. Wood J.E., Senthılmohan S.T., Peskın A.V. Antioxidant Activity of Procyanidin-Containing Plant Extract at Different Phs. Food Chem. 2002, 77, 155-161.
  • [39]. Kılcıgil G.A., Kuş C., Özdamar E. D., Eke B.C., İşcan M. Synthesis and Antioxidant Capacities of Some New Benzimidazole Derivatives. Arch Pharm [Weinheim] 2007, 340, 607-611.
There are 39 citations in total.

Details

Journal Section Natural Sciences
Authors

Serap Şahin Bölükbaşı

Neslihan Şahin

Publication Date December 8, 2017
Submission Date May 12, 2017
Acceptance Date August 28, 2017
Published in Issue Year 2017

Cite

APA Şahin Bölükbaşı, S., & Şahin, N. (2017). Synthesis, Characterization and In Vitro Antioxidant Activities of New Benzimidazole Ruthenium- (II) Complexes. Cumhuriyet Science Journal, 38(4), 738-747. https://doi.org/10.17776/csj.349326