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Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives

Year 2017, Volume: 2 Issue: 2, 165 - 170, 30.12.2017

Yusuf Sıcak

Abstract

In this study was aimed to investigate antioxidant, anticholinesterase inhibitory, tyrosinase inhibitory and urease inhibitory activities of the synthesized fifteen hydrazone compounds (1-15). According to the antioxidant activity assay results, compound 8 (IC50= 22.40±0.87 μM) and 6 (IC50= 29.48±0.71 μM) showed the best lipid peroxidation inhibitory activity. The compound 6 and 8 exhibited better activity IC50 value of 21.34±0.11 and 25.33±0.27 μM, respectively, than standard BHT (IC50= 54.97±0.99 μM) in DPPH free scavenging activity. Among the tested compound, compound 6 (IC50= 11.71±0.28 μM) and 8 (IC50= 16.45±0.31 μM) showed the best cation radical scavenging activity. Compound 6, 11, 10, 8, 1, 7, and 14 indicated the best CUPRAC capacity activity with an A0.5 value of 15.12±0.00, 17.91±0.01, 21.18±0.00, 23.25±0.03, 24.29±0.01, 26.83±0.01, and 32.35±0.02 μM, respectively, than the standard antioxidants, α-tocopherol (A0.5=40.55±0.04 μM) and BHA (A0.5=32.71±0.02 μM) using as standards. Compound 14 (IC50=11.38±0.44 μM) and 6 (IC50=18.77±0.61 μM) showed the highest acetylcholinesterase inhibitory activity. Among them, compound 2, 14, 6, 3, 13, 8, 10, 11, and 12 were determined to have butyrylcholinesterase inhibitory activity IC50 value of 24.12±0.65, 27.46±0.44, 29.33±0.21, 30.26±0.05, 35.60±0.53, 37.42±0.48, 39.44±0.74, 42.75±0.22, and 45.40±0.76 μM, respectively, than the standard galantamine (IC50=44.03±0.14 μM). According to the tyrosinase assay results, compound 3 (IC50=12.20±0.44 mM), 4 (IC50=14.76±0.90 mM), 15 (IC50=16.28±0.41 mM), 5 (IC50=18.39±0.87 mM), and 2 (IC50=20.12±0.33 mM) exhibited the best tyrosinase inhibitory activity. Compound 6 (IC50=19.20±0.48 mM) and 14 (IC50=22.62±0.38 μM) founded that the urease inhibitory activity are significant when compared with the thiourea (IC50=23.08±0.19 μM).

Keywords

Hydrazone antioxidant activity tyrosinase inhibitory activity urease inhibitory activity anticholinesterase inhibitory activity

References

  • Abou Ouf AA, El-Kerdawy MM, Selim HA. 1973. Synthesis of N4-(α-thiophenesulfonyl)semicarbazides and semicarbazones. Journal of Drug Research, 5/1:127-134.
  • Apak R, Güçlü K, Özyürek M, Karademir SE. 2004. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, Using their cupric ion reducing capacity in the presence of neocuproine: Cuprac Method. J Agric Food Chem, 52:7970-7981.
  • Blois MS.1958. Antioxidant determinations by the use of a stable free radical. Nature, 181: 1199-1200.
  • Bonde CG, Peepliwal A, Gaikwad NJ. 2010. Synthesis and Antimycobacterial of Azetidine-, Quinazoline-, and Triazolo-thiadiazole-containing Pyrezines. Archive Der Pharmazie Chemistry in Life Sciences, 343: 228-236.
  • Bower JD, Doyle FP. 1957. Preparation of fused triazole systems. J Chem Society, 727-732.
  • Dimmock JR, Vashishtha SC, Stables JP. 1999. Anticonvulsant properties of various acetylhydrazones, oxamoylhydrazones and semicarbazones derived from aromatic and unsaturated carbonyl compounds. Eur J Med Chem, 35: 241-248.
  • Ellman GL, Courtney KD, Andres V, Featherstone RM. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol Behaivor, 7:88-95.
  • El-Sabbagh OI, Rady HM. 2009. Synthesis of new acridines and hydrazones derived from cyclic β-diketone for cytotoxic and antiviral evaluation. Eur J Med Chem, 44:3680-3686.
  • Emilsson H, Selander H. 1988. Synthesis and antihypertensive activity of substituted (2,6-dichlorobenzylideneamino) guanidines and some hydrazone derivatives of C-cyanoformamidrazone. Acta Pharm Suec, 25(2): 75-86.
  • Ergenç N, Günay NS. 1998. Synthesis and antidepressant evaluation of new 3-phenyl-5-sulfonamidoindole derivatives. Eur J Med Chem, 33:143-148.
  • Franzen H, Eichler T. 1911. Benzalhydrazines. Journal fuer Prktische Chemie (Leipzing), 82: 241-251.
  • Gürsoy E, Güzeldemirci-Ulusoy N. 2007. Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives. Eur J Med Chem, 42: 320-326.
  • Hearing VJ. 1987. Methods in Enzymology. Academic Press: New York, 142: 154-165.
  • Kern W, Hucke T, Hollander R, Schneider R. 1957. Hydrazides of poly(acrylic acids). I. Makromolekulare Chemie, 22:31-38.
  • Khatib S, Nerya O, Musa R, Shumel M, Tamir S, Vaya J. 2005. Chalcones as Potent Tyrosinase Inhibitors: The Importance of 2,4-disubstituted Resorcinol Moiety. Bioorg Med Chem, 13/13:433-441.
  • Maaskant L. 1937. Chloro- and bromo-nitrophenylhydrazines and methylhydrazines and their derivatives. Recueil des Travaux Chiniques des Pays-Bas et de la Belgique, 56:211-232.
  • Meister W. 1908. Constitution of Methazonic Acid. Berichte der Deutschen Chemischen Gesellschaft, 40:3435-3449.
  • Melnyk P, Leorux V, Sergheraert C, Grellier P. 2006. Desing, synthesisand in vitro antimalaryal activity of an acylhydrazone library. Bioorg Med Chem, 16:31-35.
  • Miller HM. 1971. A simplified method for the evaluation of antioxidants. J Am Oil Chem Soc, 48:91.
  • Niyaz NM, Guenthenspberger KA, Hunter R, Brown AV, Nugent JS. 2009. Preparation of insecticidal (1,3,5)-triazinyl phenyl hydrazones. US 20090093481.
  • Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. 1989. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Rad Bio Med, 26:1231-1237.
  • Reed HS, Dufrenoy J, Parikh JR, Oneto JF. 1950. Effects on grape cuttings of two new chemical growth regulators in relation to nitrogenous nutrition. Compt Rend, 230: 2317-2318.
  • Rollas S, Gülerman N, Erdeniz H. 2002. Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines. Il Farmaco, 57:171-174.
  • Salgın-Gökşen U, Gökhan-Kelekçi N, Göktaş Ö, Köysal Y, Kılıç E, Işık Ş, Aktay G, Özalp M. 2007. 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg Med Chem, 15:5738-5751.
  • Shastin AV, Korotchenko VN, Nenajdenko VG, Balenkova ES. 2001. A novel synthesis of β,β-dibromostyrenes. Synthesis, 14:2081-2084.
  • Stroh HH. 1957. Asymmetric methyltolylhydrazines and their reactions with sugars. Chemische Berichte, 90:352-357.
  • Takase A, Kai H. 1997. Preparation of alpha-alkoxyiminobenzyl heterocyclic derivatives as pesticides. WO 9712875.
  • Todeschini AR, Miranda AL, Silva CM, Parrini SC, Barreiro EJ. 1998. Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives. Eur J Med Chem, 33:189-199.
  • Troger J, Lange G. 1920. o-, m-, and p-Tolylazo-α-naphthylhydrazinosulfonic acids. Journal feur Prktische Chemie (Leipzig), 101:123-135.
  • Tuktarov AR, Khuzin AA, Korolev VV, Dzhemilev UM. 2012. Catalytic cycloaddition of diazoalkanes with heterocyclic substituents to fullerene C60. Russian Journal of Organic Chemistry, 48/1:99-103.
  • Vicini P, Zani F, Cozzini P, Doytchinova I. 2002. Hydrazones of 1,2-benzisothiazole hydrazides: synthesis, antimicrobial activity and QSAR investigations. Eur J Med Chem, 37:553-564.
  • Weatherburn MW. 1967. Phenol- hypochlorite reaction for determination of ammonia. Analy Chem, 39:971-974.
  • Yoneda F, Kawamura M, Nagamatsu T, Kuretani K, Hoshi A, Iigo M. 1976. A transformation of 7-azapteridines into 6-azapurines (imidazo[4,5-e]-as-triazines). Heterocycles, 4/9:1503-1508.

Bazı Hidrazon Türevlerinin Antioksidan, Antikolinesteraz İnhibisyon, Tirozinaz İnhibisyon ve Üreaz İnnhibisyon Aktivitelerinin Araştırılması

Year 2017, Volume: 2 Issue: 2, 165 - 170, 30.12.2017

Yusuf Sıcak

Abstract

Bu çalışmada, 15 hidrazon molekülünün (1-15) antioksidan, antikolinesteraz inhibisyon, tirozinaz inhibisyon ve üreaz inhibisyon aktivitelerinin araştırılması amaçlandı. Antioksidan aktivite test sonuçlarına göre, 8 (IC50=22.40±0.87 μM) ve 6 (IC50=29.48±0.71 μM) numaralı moleküller en iyi lipit peroksidaz inhibisyon aktivitesine sahip olduğunu gösterdi. 6 ve 8 numaralı moleküllerin DPPH serbest radikal giderim aktivitesi, standart BHT’ya (IC50=54.97±0.99 μM) göre sırasıyla 21.34±0.11 ve 25.33±0.27 μM’lik IC50 değerleri ile test edilen moleküllere istinaden daha iyi aktivite sergilediği saptandı. Test edilen moleküller arasında 6 (IC50=11.71±0.28 μM) ve 8 (IC50=16.45±0.31 μM) numaralı moleküllerin en iyi katyon radikal giderim aktivitesine sahip olduğunu bulundu. 6, 11, 10, 8, 1, 7 ve 14 numaralı moleküller α-tokoferol (A0.5=40.55±0.04 μM) ve BHA (A0.5=32.71±0.02 μM) antioksidan standartlarına göre 15.12±0.00, 17.91±0.01, 21.18±0.00, 23.25±0.03, 24.29±0.01, 26.83±0.01 ve 32.35±0.02 μM’lik A0.5 değerleriyle en iyi CUPRAC kapasite aktivitesine sahip olduğu saptandı. 14 (IC50=11.38±0.44 μM) ve 6 (IC50=18.77±0.61 μM) numaralı moleküller en iyi asetilkolinesteraz inhibisyon aktivitesi sergilerken, 2, 14, 6, 3, 13, 8, 10, 11 ve 12 numaralı moleküllerin ise BChE standardı olarak kullanılan galantamine (IC50=44.03±0.14 μM) göre sırasıyla 24.12±0.65, 27.46±0.44, 29.33±0.21, 30.26±0.05, 35.60±0.53, 37.42±0.48, 39.44±0.74, 42.75±0.22, and 45.40±0.76 μM’lik IC50 değerleriyle en iyi butirilkolinesteraz inhibisyon aktivitesine sahip oldukları belirlendi. Tiroazinaz test sonuçlarına göre, 3 (IC50=12.20±0.44 mM), 4 (IC50=14.76±0.90 mM), 15 (IC50=16.28±0.41 mM), 5 (IC50=18.39±0.87 mM), ve 2 (IC50=20.12±0.33 mM) numaralı moleküllerin en iyi tirozinaz inhibisyon aktivitesi sergilendiği bulundu. Test edilen hidrazon moleküllerinin üreaz inhibisyon aktivitesi standart olarak kullanılan tiyoüre (IC50=23.08±0.19 μM) ile mukayese edilediğinde 6 (IC50=19.20±0.48 mM) ve 4 (IC50=22.62±0.38 μM) numaralı hidrazon moleküllerinin daha iyi olduğu tespit edildi.

Keywords

Hidrazon antioksidan aktivite antikolinesteraz inhibisyon aktivite tirozinaz inhibisyon aktivite üreaz inhibisyon aktivite

References

  • Abou Ouf AA, El-Kerdawy MM, Selim HA. 1973. Synthesis of N4-(α-thiophenesulfonyl)semicarbazides and semicarbazones. Journal of Drug Research, 5/1:127-134.
  • Apak R, Güçlü K, Özyürek M, Karademir SE. 2004. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, Using their cupric ion reducing capacity in the presence of neocuproine: Cuprac Method. J Agric Food Chem, 52:7970-7981.
  • Blois MS.1958. Antioxidant determinations by the use of a stable free radical. Nature, 181: 1199-1200.
  • Bonde CG, Peepliwal A, Gaikwad NJ. 2010. Synthesis and Antimycobacterial of Azetidine-, Quinazoline-, and Triazolo-thiadiazole-containing Pyrezines. Archive Der Pharmazie Chemistry in Life Sciences, 343: 228-236.
  • Bower JD, Doyle FP. 1957. Preparation of fused triazole systems. J Chem Society, 727-732.
  • Dimmock JR, Vashishtha SC, Stables JP. 1999. Anticonvulsant properties of various acetylhydrazones, oxamoylhydrazones and semicarbazones derived from aromatic and unsaturated carbonyl compounds. Eur J Med Chem, 35: 241-248.
  • Ellman GL, Courtney KD, Andres V, Featherstone RM. 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol Behaivor, 7:88-95.
  • El-Sabbagh OI, Rady HM. 2009. Synthesis of new acridines and hydrazones derived from cyclic β-diketone for cytotoxic and antiviral evaluation. Eur J Med Chem, 44:3680-3686.
  • Emilsson H, Selander H. 1988. Synthesis and antihypertensive activity of substituted (2,6-dichlorobenzylideneamino) guanidines and some hydrazone derivatives of C-cyanoformamidrazone. Acta Pharm Suec, 25(2): 75-86.
  • Ergenç N, Günay NS. 1998. Synthesis and antidepressant evaluation of new 3-phenyl-5-sulfonamidoindole derivatives. Eur J Med Chem, 33:143-148.
  • Franzen H, Eichler T. 1911. Benzalhydrazines. Journal fuer Prktische Chemie (Leipzing), 82: 241-251.
  • Gürsoy E, Güzeldemirci-Ulusoy N. 2007. Synthesis and primary cytotoxicity evaluation of new imidazo[2,1-b]thiazole derivatives. Eur J Med Chem, 42: 320-326.
  • Hearing VJ. 1987. Methods in Enzymology. Academic Press: New York, 142: 154-165.
  • Kern W, Hucke T, Hollander R, Schneider R. 1957. Hydrazides of poly(acrylic acids). I. Makromolekulare Chemie, 22:31-38.
  • Khatib S, Nerya O, Musa R, Shumel M, Tamir S, Vaya J. 2005. Chalcones as Potent Tyrosinase Inhibitors: The Importance of 2,4-disubstituted Resorcinol Moiety. Bioorg Med Chem, 13/13:433-441.
  • Maaskant L. 1937. Chloro- and bromo-nitrophenylhydrazines and methylhydrazines and their derivatives. Recueil des Travaux Chiniques des Pays-Bas et de la Belgique, 56:211-232.
  • Meister W. 1908. Constitution of Methazonic Acid. Berichte der Deutschen Chemischen Gesellschaft, 40:3435-3449.
  • Melnyk P, Leorux V, Sergheraert C, Grellier P. 2006. Desing, synthesisand in vitro antimalaryal activity of an acylhydrazone library. Bioorg Med Chem, 16:31-35.
  • Miller HM. 1971. A simplified method for the evaluation of antioxidants. J Am Oil Chem Soc, 48:91.
  • Niyaz NM, Guenthenspberger KA, Hunter R, Brown AV, Nugent JS. 2009. Preparation of insecticidal (1,3,5)-triazinyl phenyl hydrazones. US 20090093481.
  • Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. 1989. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Rad Bio Med, 26:1231-1237.
  • Reed HS, Dufrenoy J, Parikh JR, Oneto JF. 1950. Effects on grape cuttings of two new chemical growth regulators in relation to nitrogenous nutrition. Compt Rend, 230: 2317-2318.
  • Rollas S, Gülerman N, Erdeniz H. 2002. Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines. Il Farmaco, 57:171-174.
  • Salgın-Gökşen U, Gökhan-Kelekçi N, Göktaş Ö, Köysal Y, Kılıç E, Işık Ş, Aktay G, Özalp M. 2007. 1-Acylthiosemicarbazides, 1,2,4-triazole-5(4H)-thiones, 1,3,4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: Synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg Med Chem, 15:5738-5751.
  • Shastin AV, Korotchenko VN, Nenajdenko VG, Balenkova ES. 2001. A novel synthesis of β,β-dibromostyrenes. Synthesis, 14:2081-2084.
  • Stroh HH. 1957. Asymmetric methyltolylhydrazines and their reactions with sugars. Chemische Berichte, 90:352-357.
  • Takase A, Kai H. 1997. Preparation of alpha-alkoxyiminobenzyl heterocyclic derivatives as pesticides. WO 9712875.
  • Todeschini AR, Miranda AL, Silva CM, Parrini SC, Barreiro EJ. 1998. Synthesis and evaluation of analgesic, antiinflammatory and antiplatelet properties of new 2-pyridylarylhydrazone derivatives. Eur J Med Chem, 33:189-199.
  • Troger J, Lange G. 1920. o-, m-, and p-Tolylazo-α-naphthylhydrazinosulfonic acids. Journal feur Prktische Chemie (Leipzig), 101:123-135.
  • Tuktarov AR, Khuzin AA, Korolev VV, Dzhemilev UM. 2012. Catalytic cycloaddition of diazoalkanes with heterocyclic substituents to fullerene C60. Russian Journal of Organic Chemistry, 48/1:99-103.
  • Vicini P, Zani F, Cozzini P, Doytchinova I. 2002. Hydrazones of 1,2-benzisothiazole hydrazides: synthesis, antimicrobial activity and QSAR investigations. Eur J Med Chem, 37:553-564.
  • Weatherburn MW. 1967. Phenol- hypochlorite reaction for determination of ammonia. Analy Chem, 39:971-974.
  • Yoneda F, Kawamura M, Nagamatsu T, Kuretani K, Hoshi A, Iigo M. 1976. A transformation of 7-azapteridines into 6-azapurines (imidazo[4,5-e]-as-triazines). Heterocycles, 4/9:1503-1508.
There are 33 citations in total.

Details

Primary Language English
Journal Section 2017-Articles
Authors

Yusuf Sıcak 0000-0003-2339-5837

Publication Date December 30, 2017
Acceptance Date December 29, 2017
Published in Issue Year 2017 Volume: 2 Issue: 2

Cite

APA Sıcak, Y. (2017). Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives. Turkish Journal of Life Sciences, 2(2), 165-170.
AMA Sıcak Y. Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives. TJLS. December 2017;2(2):165-170.
Chicago Sıcak, Yusuf. “Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives”. Turkish Journal of Life Sciences 2, no. 2 (December 2017): 165-70.
EndNote Sıcak Y (December 1, 2017) Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives. Turkish Journal of Life Sciences 2 2 165–170.
IEEE Y. Sıcak, “Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives”, TJLS, vol. 2, no. 2, pp. 165–170, 2017.
ISNAD Sıcak, Yusuf. “Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives”. Turkish Journal of Life Sciences 2/2 (December 2017), 165-170.
JAMA Sıcak Y. Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives. TJLS. 2017;2:165–170.
MLA Sıcak, Yusuf. “Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives”. Turkish Journal of Life Sciences, vol. 2, no. 2, 2017, pp. 165-70.
Vancouver Sıcak Y. Investigation of Antioxidant, Anticholinesterase Inhibitory, Tyrosinase Inhibitory and Urease Inhibitory Activities of Some Hydrazone Derivatives. TJLS. 2017;2(2):165-70.
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