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Laktoperoksidaz Enziminin Sülfamat Türevleri Bileşikleri Üzerine İnhibisyon Profili

Year 2020, Issue: 20, 746 - 750, 31.12.2020
https://doi.org/10.31590/ejosat.767395

Abstract

Sülfamat iskeleti içeren birçok doğal ürün ve ilaç etken maddelerinde bulunmaktadırlar. Son zamanlarda, sülfamatlar bileşiklerinin bulundurdukları fonksiyonel gruplarından dolayı malzeme bilimcisi ve farmakolog tarafından daha fazla ilgi görmektedirler. Peroksidazlar (POD), metabolik fonksiyonlarından dolayı gıda ve ilaç endüstrisinde enzimatik reaksiyonlarda ve klinik teşhislerde önemli kullanım alanında yer alırlar. Laktoperoksidaz (LPO, EC 1.11.1.7 ) peroksidaz ailesinin bir üyesidir. Bu enzim sütte, tükürükte ve gözyaşında bulunan bir oksidoredüktaz olup, patojen mikroorganizmalara karşı yeni doğanların bağırsak sistemlerini ve meme bezlerini korumada önemli bir role sahiptir. Memeli sütlerinden edilen LPO enzimi, bakterilerin büyümesinin baskılanmasında ve bakteri inhibisyonunun desteklenmesinde oldukça önemlidir. Sığır LPO’sunun bakteriyal büyümeyi inhibe etmesi, H2O2 ve tiyosiyanat içeren peroksidaz sistemine atfedilir. Bu sistemin antimikrobiyal etkisi sütte doğal olarak oluşur. LPO enzimi üzerine yapılan antibakteriyal çalışmalarda LPO-tiyosiyanat ve peroksit sisteminin patajonik bakterilerde önemli derecede inhibisyona sebep olduğu tespit edilmiştir. LPO’nun birçok uygulama alanı vardır. Peroksidazlar hem gıdalarda hem de farmakolojik uygulamalarda koruyucu olarak kullanılabilmekte ve süt işleme tesislerinde nakil esnasında sütün muhafazası amacıyla süt endüstrisinde kullanılmaktadır. Bu çalışmanın amacı, LPO enzimi üzerine Metil benzoilsülfamat, Metil (2-bromobenzoil)sülfamat, Metil (3-fenilpropanoil)sülfamat, Metil (1-naphthoil)sülfamat, Metil (2-metilbenzoil)sülfamat, Metil (2-iyodobenzoil)sülfamat, Metil (2-fenilbutanoil)sülfamat, Metil (4-isopropilbenzoil)sülfamat, Metil (4-metoksibenzoil)sülfamat ve Metil (isoquinoline-1-karbonil)sülfamat bileşilklerinin in vitro etkilerini belirlemektir. Bu sülfamat türevi bileşiklerinin LPO enzimi üzerindeki inhibisyon etkisini belirlemek için, enzim aktiviteleri ölçülerek her bir inhibitör için Lineweaver-Burk grafikleri çizildi; Ki sabiti ve inhibisyon tipleri bu çizilen grafiklerden hesaplandı. Ki değerleri sırasıyla Metil benzoilsülfamat 0,70 μM, Metil (2-bromobenzoil)sülfamat 0,025 μM, Metil (3-fenilpropanoil)sülfamat 0,018 μM, Metil (1-naphthoil)sülfamat 0,047 μM, Metil (2-metilbenzoil)sülfamat 0,043 μM, Metil (2-iyodobenzoil)sülfamat 0,19 μM, Metil (2-fenilbutanoil)sülfamat 0,39 μM, Metil (4-isopropilbenzoil)sülfamat 0,42 μM, Metil (4-metoksibenzoil)sülfamat 0,078 μM, Metil (isoquinoline-1-karbonil)sülfamat 0,075 μM olarak belirlendi. Metil (4-isopropilbenzoil)sülfamat bileşiği yarışmasız inhibisyon ve diğer maddeler yarışmalı inhibisyon gösterdiği kaydedildi. Metil (2-metilbenzoil)sülfamat bileşiği ise en etkili inhibitör özelliğini yarışmalı inhibisyon tipi LPO enzimi üzerine 0.018 ± 0.024 μM Ki değeri ile göstermiştir.

Supporting Institution

sinop üniversitesi

References

  • Albright, J.D., Devries, V.G., Du, M.T., Largis, E.E., Miner, T.G., Reich, M.F., Shepherd, R.G. (1983). Potential antiatherosclerotic agents. 2. (Aralkylamino)- and (alkylamino)benzoic acid analogs of cetaben J. Med. Chem. 26 1393e1411.
  • Atamer M, Kocak C, Cimer A, Odabasi S, Tamucay B, Yamaner N. (1999). Some quality characteristics of Kasar cheese manufactured from milk preserved by activation of lactoperoxidase/thiocyanate/hydrogen peroxide (LP) system. Milchwissenschaft, 54: 553–556.
  • Atmaca, U. (2019). Efficient and one-pot synthesis of novel sulfamates from carboxylic acids. Tetrahedron 75 (34), 130467. Atmaca, U. (2020) Tek Kapta Yeni Bir Yöntemle Alkollerden Potansiyel Biyolojik Aktif Azidosülfonil Bileşiklerinin Sentezi. Journal of the Institute of Science and Technology. 0(1): 345-356.
  • Berg, J.M., Tymoczko, J.L., Stryer, L. (2014). Biyokimya. Palme Yayıncılık, 241-247p, Ankara.
  • Booth, KS, Kimura, S., Lee, HC., Ikeda-Saito, M., & Caughey, WS. (1989). Bovine myeloperoxidase and lactoperoxidase each contain a high affinity binding site for calcium. Biochemical and Biophysical Research Communications. 160, 879±902.
  • Champe, P.C., Harvey, R.A., Ferrier, D.R. (2007). Lippincott’s lllustrated Reviews Serisinden: Biyokimya. Nobel Tıp Kitapevleri, Bursa
  • Daryadel S, Atmaca U, Taslimi P, Gulcin I, Celik M. (2018). Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties. Archiv Der Pharmazie. 351.
  • Davies, KJ. (1995). Oxidative stress: the paradox of aerobic life. Biochem Soc Symp.61:1–31.
  • de Wit JN, van Hooydonk ACM. (1996). Structure, functions and applications of lactoperoxidase in natural antimicrobial systems. Netherlands Milk & Dairy Journal. 50: 227±244.
  • Demir Y, Beydemir Ş. (2015). Purification, refolding, and characterization of recombinant human paraoxonase-1. Turkish Journal of Chemistry. 39(4): 764-776.
  • Elagamy, E., Ruppanner, R., Ismail, A., Champagne, C.P., and Assal, R. (1992). Antibacterial and antiviral activity of camel milk protective proteins. J. Dairy. Res. 59, 169-175.
  • Goddard-Borger ED, Stick RV. (2007). An efficient, inexpensive, and shelf-stable diazotransfer reagent: Imidazole-1-sulfonyl azide hydrochloride. Organic Letters. 9: 3797-800
  • Gulcin I, Mshvildadze V, Gepdiremen A, Elias R. (2006). Screening of antioxidant and antiradical activity of monodesmosides and crude extract from Leontice smirnowii Tuber. Phytomedicine. 13: 343–351.
  • Haddain MS, Ibrahim SA, Robinson RK. (1996). Preservation of raw milk by activation of the natural lactoperoxidase systems. Food Control. 7: 149–152.
  • Gülçin, İ., Kirecci, E., Akkemik, E., Topal, F., Hisar, O. (2010a). Antioxidant and Antimicrobial Activities of an Aquatic Plant: Duckweed (Lemna minor L.). Turkish Journal of Agriculture and Forestry. 34, 175-188.
  • Haddain, M.S., İbrahim, S.A., and Robinson, R.K. (1996). Preservation of raw milk by activation of the natural lactoperoxidase systems. Food Control. 7, 149-152.
  • Hartwig JF. (1998). Carbon-heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides. Accounts of Chemical Research. 31: 852-60.
  • Hussain S, Slikker W, Ali SF. (1995). Age related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different region of mouse brain. International Journal of Developmental Neuroscience.13: 811–817.
  • Ilardi, E.A. Vitaku, E. Njardarson, J.T. (2014). J. Med. Chem. 57, 2832e2842.
  • Jacob BM, Monoj NK, Haridas M. (1998). Antibacterial property of goat milk lactoperoxidase. Indian Journal of Experimental Biology. 31: 808.
  • Kumar R, Bhatla KL. (1995). Purification, crystallization and preliminary x-ray crystallographic analysis of lactoperoxidase from buffalo milk. Acta Crystallographica. 51: 1094.
  • Kussendrager KD, van Hooijdonk ACM. (2000). Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. British Journal of Nutrition. 84: 19–25.
  • Lehninger, A.L., Nelson, D.L., Cox, M.M. (2005). Principles of biochemistry, 3. Baskıdan çeviri (Çeviri editörü: Kılıç N.), Palme Yayıncılık.
  • Llaverias, G., Laguna, J.C. Alegret, M. Cardiovasc. (2003) Drug Rev. 21, 33e50
  • Paul, K.G., and Ohlsson, P.I. (1985). In the Lactoperoxidase System: Pruitt KM, and Tenovue YO, (Eds.) Chemistry and Biological Significance, New York, USA: Marcel Dekker Inc. p.15-29.
  • Peterson, E.M., Brownell, J., Vince, R. (1992). J. Med. Chem. 35, 3991e4000.
  • Pütter, J., and Becker, R. (1987), Methods of Enzymatic Analysis: Peroxidases Bergmeyer, third edition, VCH ,New York, s.286.
  • Reiter, B., & HaÈrnulv, G. (1984). Lactoperoxidase antibacterialsystem: natural occurrence, biological functions and practical applications. Journal of Food Protection, 47, 724±732.
  • Reiter, B., & Perraudin, JP. (1991). Lactoperoxidase: biological functions. In Peroxydases in Chemistry and Biology. pp. 143± 180. Boca Raton: CRC Press.
  • Sharma, S., Singh, A. K., Kaushik, S., Sinha, M., Singh, R. P., et al. (2013). Lactoperoxidase structural insights into the function, ligand binding and inhibition. International journal of biochemistry and molecular biology. 4(3), 108.
  • Shindler, J.S., and Bardsley, W.G. (1975). Steady-state kinetics of lactoperoxidase with ABTS as chromogen. Biochem. and Biophys. Res. Comm. 67, 1307.
  • Sisecioğlu M, Cankaya M, Ozdemir H. (2009). Effects of some vitamins on lactoperoxidase enzyme activity. Internatıonal Journal for Vitamin and Nutrition Research. 79: 188–194.
  • Sisecioglu, M., Gulcin, I., Cankaya, M., Atasever, A., & Ozdemir, H. (2010). The effects of norepinephrine on lactoperoxidase enzyme. Scientific Research and Essays. 5,1351–1356.
  • Thanabal, V., & La Mar, GN. (1989) A nuclear Overhauser effect investigation of the molecular and electronic structure of the heme crevice in lactoperoxidase. Biochemistry, 28, 7038±7044.
  • Uguz, M.T., & Ozdemir, H. (2005). Purification of bovine milk lactoperoxidase and nvestigation of antibacterial properties at different thiocyanate mediated. Applied. Biochemistry andMicrobiology. 41, 397–401.
  • Van Huystee, R.B. (1987). Some moleculer aspects of plant peroxidase biosynthetic studies. Ann. Rev. Plant. Physiol, 38, 205.
  • Wolfson, LM., & Sumner, SS. (1993). Antimicrobial activity of the lactoperoxidase system. A review. Journal of Food Protection. 56, 887±892.

Inhibition Profile of Lactoperoxidase Enzyme on Sulfamate Derivatives

Year 2020, Issue: 20, 746 - 750, 31.12.2020
https://doi.org/10.31590/ejosat.767395

Abstract

They are found in many natural products and active ingredients that contain a sulfamate skeleton. Recently, due to the functional groups of sulfamates compounds, they have received more attention from the material scientist and pharmacologist. Due to their metabolic functions, peroxidases (POD) are important in enzymatic reactions and clinical diagnoses in the food and pharmaceutical industry. Lactoperoxidase (LPO, EC 1.11.1.7) is a member of the peroxidase family. This enzyme is an oxidoreductase found in milk, saliva and tears and has an important role in protecting the gut systems and mammary glands of newborns against pathogenic microorganisms. The LPO enzyme from mammalian milk is very important in suppressing the growth of bacteria and promoting bacterial inhibition. Inhibition of bacterial growth of bovine LPO is attributed to the peroxidase system containing H2O2 and thiocyanate. The antimicrobial effect of this system occurs naturally in milk. In antibacterial studies on LPO enzyme, LPO-thiocyanate and peroxide system has been found to cause a significant inhibition of pathogenic bacteria. LPO has many application areas. Peroxidases can be used as preservatives in both food and pharmacological applications, and are used in the milk industry for milk preservation during transport in milk processing plants. The aim of this study is to determine the in vitro effects of Methyl benzoylsulfamate, Methyl (2-bromobenzoyl) sulfamate, Methyl (3-phenylpropanoyl) sulfamate, Methyl (1-naphthoyl) sulfamate, Methyl (2-methylbenzoyl) sulfamate, Methyl (2-iodobenzoyl) sulfamate, Methyl (2-phenyl), Methyl (4-isopropylbenzoyl) sulfamate, Methyl (4-methoxybenzoyl) sulfamate and Methyl (isoquinoline-1-carbonyl) sulfamate compounds on LPO enzyme. To determine the inhibition effect of these sulfamate derivative compounds on the LPO enzyme, Lineweaver-Burk plots were drawn for each inhibitor by measuring enzyme activities; Ki constant and inhibition types were calculated from these plotted graphs. Ki values were determined as Methyl benzoylsulfamate 0.70 μM, Methyl (2-bromobenzoyl) sulfamate 0.025 μM, Methyl (3-phenylpropanoyl) sulfamate 0.018 μM, Methyl (1-naphthoyl) sulfamate 0.047 μM, Methyl (2-methylbenzoyl) sulfamate 0.043 μM, Methyl (2-methylbenzoyl) sulfamate 0.043 μM -Iodobenzoyl) sulfamate 0.19 μM, Methyl (2-phenylbutanoyl) sulfamate 0.49 μM, Methyl (4-isopropylbenzoyl) sulfamate 0.42 μM, Methyl (4-methoxybenzoyl) sulfamate 0.078 μM, Methyl (isoquinoline-1-carbonyl ) sulfamate 0.075 μM, respectively. Methyl (4-isopropylbenzoyl) sulfamate compound was noted to exhibit non-competitive inhibition and other substances showed competitive inhibition. Methyl (2-methylbenzoyl) sulfamate compound, on the other hand, showed its most effective inhibitory feature on competitive competitive inhibition type LPO enzyme with a value of Ki 0.018 ± 0.024 μM.

References

  • Albright, J.D., Devries, V.G., Du, M.T., Largis, E.E., Miner, T.G., Reich, M.F., Shepherd, R.G. (1983). Potential antiatherosclerotic agents. 2. (Aralkylamino)- and (alkylamino)benzoic acid analogs of cetaben J. Med. Chem. 26 1393e1411.
  • Atamer M, Kocak C, Cimer A, Odabasi S, Tamucay B, Yamaner N. (1999). Some quality characteristics of Kasar cheese manufactured from milk preserved by activation of lactoperoxidase/thiocyanate/hydrogen peroxide (LP) system. Milchwissenschaft, 54: 553–556.
  • Atmaca, U. (2019). Efficient and one-pot synthesis of novel sulfamates from carboxylic acids. Tetrahedron 75 (34), 130467. Atmaca, U. (2020) Tek Kapta Yeni Bir Yöntemle Alkollerden Potansiyel Biyolojik Aktif Azidosülfonil Bileşiklerinin Sentezi. Journal of the Institute of Science and Technology. 0(1): 345-356.
  • Berg, J.M., Tymoczko, J.L., Stryer, L. (2014). Biyokimya. Palme Yayıncılık, 241-247p, Ankara.
  • Booth, KS, Kimura, S., Lee, HC., Ikeda-Saito, M., & Caughey, WS. (1989). Bovine myeloperoxidase and lactoperoxidase each contain a high affinity binding site for calcium. Biochemical and Biophysical Research Communications. 160, 879±902.
  • Champe, P.C., Harvey, R.A., Ferrier, D.R. (2007). Lippincott’s lllustrated Reviews Serisinden: Biyokimya. Nobel Tıp Kitapevleri, Bursa
  • Daryadel S, Atmaca U, Taslimi P, Gulcin I, Celik M. (2018). Novel sulfamate derivatives of menthol: Synthesis, characterization, and cholinesterases and carbonic anhydrase enzymes inhibition properties. Archiv Der Pharmazie. 351.
  • Davies, KJ. (1995). Oxidative stress: the paradox of aerobic life. Biochem Soc Symp.61:1–31.
  • de Wit JN, van Hooydonk ACM. (1996). Structure, functions and applications of lactoperoxidase in natural antimicrobial systems. Netherlands Milk & Dairy Journal. 50: 227±244.
  • Demir Y, Beydemir Ş. (2015). Purification, refolding, and characterization of recombinant human paraoxonase-1. Turkish Journal of Chemistry. 39(4): 764-776.
  • Elagamy, E., Ruppanner, R., Ismail, A., Champagne, C.P., and Assal, R. (1992). Antibacterial and antiviral activity of camel milk protective proteins. J. Dairy. Res. 59, 169-175.
  • Goddard-Borger ED, Stick RV. (2007). An efficient, inexpensive, and shelf-stable diazotransfer reagent: Imidazole-1-sulfonyl azide hydrochloride. Organic Letters. 9: 3797-800
  • Gulcin I, Mshvildadze V, Gepdiremen A, Elias R. (2006). Screening of antioxidant and antiradical activity of monodesmosides and crude extract from Leontice smirnowii Tuber. Phytomedicine. 13: 343–351.
  • Haddain MS, Ibrahim SA, Robinson RK. (1996). Preservation of raw milk by activation of the natural lactoperoxidase systems. Food Control. 7: 149–152.
  • Gülçin, İ., Kirecci, E., Akkemik, E., Topal, F., Hisar, O. (2010a). Antioxidant and Antimicrobial Activities of an Aquatic Plant: Duckweed (Lemna minor L.). Turkish Journal of Agriculture and Forestry. 34, 175-188.
  • Haddain, M.S., İbrahim, S.A., and Robinson, R.K. (1996). Preservation of raw milk by activation of the natural lactoperoxidase systems. Food Control. 7, 149-152.
  • Hartwig JF. (1998). Carbon-heteroatom bond-forming reductive eliminations of amines, ethers, and sulfides. Accounts of Chemical Research. 31: 852-60.
  • Hussain S, Slikker W, Ali SF. (1995). Age related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different region of mouse brain. International Journal of Developmental Neuroscience.13: 811–817.
  • Ilardi, E.A. Vitaku, E. Njardarson, J.T. (2014). J. Med. Chem. 57, 2832e2842.
  • Jacob BM, Monoj NK, Haridas M. (1998). Antibacterial property of goat milk lactoperoxidase. Indian Journal of Experimental Biology. 31: 808.
  • Kumar R, Bhatla KL. (1995). Purification, crystallization and preliminary x-ray crystallographic analysis of lactoperoxidase from buffalo milk. Acta Crystallographica. 51: 1094.
  • Kussendrager KD, van Hooijdonk ACM. (2000). Lactoperoxidase: physico-chemical properties, occurrence, mechanism of action and applications. British Journal of Nutrition. 84: 19–25.
  • Lehninger, A.L., Nelson, D.L., Cox, M.M. (2005). Principles of biochemistry, 3. Baskıdan çeviri (Çeviri editörü: Kılıç N.), Palme Yayıncılık.
  • Llaverias, G., Laguna, J.C. Alegret, M. Cardiovasc. (2003) Drug Rev. 21, 33e50
  • Paul, K.G., and Ohlsson, P.I. (1985). In the Lactoperoxidase System: Pruitt KM, and Tenovue YO, (Eds.) Chemistry and Biological Significance, New York, USA: Marcel Dekker Inc. p.15-29.
  • Peterson, E.M., Brownell, J., Vince, R. (1992). J. Med. Chem. 35, 3991e4000.
  • Pütter, J., and Becker, R. (1987), Methods of Enzymatic Analysis: Peroxidases Bergmeyer, third edition, VCH ,New York, s.286.
  • Reiter, B., & HaÈrnulv, G. (1984). Lactoperoxidase antibacterialsystem: natural occurrence, biological functions and practical applications. Journal of Food Protection, 47, 724±732.
  • Reiter, B., & Perraudin, JP. (1991). Lactoperoxidase: biological functions. In Peroxydases in Chemistry and Biology. pp. 143± 180. Boca Raton: CRC Press.
  • Sharma, S., Singh, A. K., Kaushik, S., Sinha, M., Singh, R. P., et al. (2013). Lactoperoxidase structural insights into the function, ligand binding and inhibition. International journal of biochemistry and molecular biology. 4(3), 108.
  • Shindler, J.S., and Bardsley, W.G. (1975). Steady-state kinetics of lactoperoxidase with ABTS as chromogen. Biochem. and Biophys. Res. Comm. 67, 1307.
  • Sisecioğlu M, Cankaya M, Ozdemir H. (2009). Effects of some vitamins on lactoperoxidase enzyme activity. Internatıonal Journal for Vitamin and Nutrition Research. 79: 188–194.
  • Sisecioglu, M., Gulcin, I., Cankaya, M., Atasever, A., & Ozdemir, H. (2010). The effects of norepinephrine on lactoperoxidase enzyme. Scientific Research and Essays. 5,1351–1356.
  • Thanabal, V., & La Mar, GN. (1989) A nuclear Overhauser effect investigation of the molecular and electronic structure of the heme crevice in lactoperoxidase. Biochemistry, 28, 7038±7044.
  • Uguz, M.T., & Ozdemir, H. (2005). Purification of bovine milk lactoperoxidase and nvestigation of antibacterial properties at different thiocyanate mediated. Applied. Biochemistry andMicrobiology. 41, 397–401.
  • Van Huystee, R.B. (1987). Some moleculer aspects of plant peroxidase biosynthetic studies. Ann. Rev. Plant. Physiol, 38, 205.
  • Wolfson, LM., & Sumner, SS. (1993). Antimicrobial activity of the lactoperoxidase system. A review. Journal of Food Protection. 56, 887±892.
There are 37 citations in total.

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Hande Usanmaz 0000-0003-3851-9601

Ufuk Atmaca 0000-0002-5598-0443

Publication Date December 31, 2020
Published in Issue Year 2020 Issue: 20

Cite

APA Usanmaz, H., & Atmaca, U. (2020). Laktoperoksidaz Enziminin Sülfamat Türevleri Bileşikleri Üzerine İnhibisyon Profili. Avrupa Bilim Ve Teknoloji Dergisi(20), 746-750. https://doi.org/10.31590/ejosat.767395