Evaluation of the Antioxidant Activity of Some Imines Containing 1H-Benzimidazoles

Objectives: The in vitro antioxidant properties of some 2-(2-phenyl)-1H-benzo(d)imidazol-1-yl)-N’-(arylmethylene) acetohydrazide derivatives (1-12)were investigated in this study.Materials and Methods: The in vitro antioxidant activity of compounds 1-12 was explored by determination of rat liver microsomal nicotinamideadenine dinucleotide phosphate dependent inhibition on lipid peroxidation (LPO) levels and microsomal ethoxyresorufin O-deethylase (EROD)activity.Results: All synthesised compounds had LPO inhibitory activity (15-57%) except compound 6, which contains a thiophene ring. Almost all thecompounds displayed slightly inhibitory activity (2-20%) on EROD.Conclusion: The most active compound, 3 bearing a p-bromophenyl substituent at the second position of the benzimidazole ring, caused 57%inhibition of LPO level, while butylated hydroxytoluene showed 65% inhibition. None of the synthesised compounds had a marked inhibitory effecton EROD activity.

1H-Benzimidazol İçeren Bazı İminlerin Antioksidan Aktivitesinin Değerlendirilmesi

Amaç: Bu çalışmada, bazı 2-(2-fenil)-1H-benzo(d)imidazol-1-il)-N’-(arilmetilen) asetohidrazit türevlerinin in vitro antioksidan özellikleri araştırılmıştır. Gereç ve Yöntemler: 1-12 numaralı bileşiklerin in vitro antioksidan aktiviteleri, lipit peroksidasyon (LPO) düzeylerine sıçan karaciğer mikrozomal nikotinamid adenin dinükleotid fosfat bağımlı inhibisyonunu ve mikrozomal etoksirezorufin O-deetilaz (EROD) aktivitesinin belirlenmesiyle incelenmiştir. Bulgular: Tiyofen halkası içeren bileşik 6 dışında, sentezlenen tüm bileşikler LPO inhibitör aktivite (%15-57) göstermiştir. Hemen hemen tüm bileşikler az miktarda EROD inhibe edici aktivite (%2-20) göstermiştir. Sonuç: Benzimidazol halkasının ikinci konumunda p-bromo fenil sübstitüenti taşıyan bileşik 3, LPO seviyesinde %57 inhibisyona neden olan en aktif bileşik iken, butillenmiş hidroksitoluen %65 inhibisyon göstermiştir. Sentezlenen bileşiklerin hiçbiri EROD aktivitesi üzerinde belirgin bir inhibisyon etkisine sahip değildir

___

1. Grune T. Oxidants and antioxidant defence systems. The Handbook of Environmental Chemistry Vol. 2: Reactions, Processes; Springer, Berlin, 2005.

2. Huang D, Ou B, Prior RL. The chemistry behind antioxidant capacity assays. J Agric Food Chem. 2005;53:1841-1856.

3. Halliwell B, Chirico S. Lipid peroxidation: its mechanism, measurement, and significance. Am J Clin Nutr. 1993;57:715S-25S.

4. Cadenas E, Packer L. Handbook of Antioxidants. 2nd ed. Revised and Expanded; Marcel Dekker: New York-Basel, 2002.

5. Ayhan-Kilcigil G, Tuncbilek M, Altanlar N, Goker H. Synthesis and antimicrobial activity of some new benzimidazole carboxylates and carboxamides, Il Farmaco. 1999;54:562-565.

6. Kus C, Sozudonmez F, Altanlar N. Synthesis and antimicrobial activity of some novel 2-[4-(substituted piperazin-/piperidin-1-ylcarbonyl) phenyl]-1H-benzimidazo-le derivatives. Arch Pharm Chem Life Sci. 2009;342:54-60.

7. Han-Bo L, Wei-Wei G, Vijai Kumar RT, Cheng-He Z, Rong-Xia G. Novel amino-pyrimidinyl benzimidazoles as potentially antimicrobial agents: Design, synthesis and biological evaluation. Eur J Med Chem. 2018;143:66-84.

8. Alp M, Goker H, Brun R, Yildiz S. Synthesis and antiparasitic and antifungal evaluation of 2’-Arylsubstituted-1H,1’H- [2,5’]bisbenzimidazolyl-5- carboxamidi-nes. Eur J Med Chem. 2009;44:2002-2008.

9. Goker H, Ayhan-Kilcigil G, Tuncbilek M, Kus C, Ertan R, Kendi E, Ozbey S, Fort M, Garcia C, Farré A. Synthesis and antihistaminic H1-Activity of 1,2,5(6)-Tri-substituted benzimidazoles. Heterocycles. 1999;51:2561- 2573.

10. Al-Douh Mh, Sahib H, Osman H, Hamid S, Salhimi S. Anti-proliferation effects of benzimidazole derivatives on Hct-116 colon cancer and mcf-7 breast cancer cell Lines. Asian Pac J Cancer P. 2012;13:4075-4079.

11. Yadav S, Sinha D, Sing KS, Singh K. Novel benzimidazole analogs as ınhibitors of EGFR tyrosine kinase. Chem Biol Drug Des. 2012;80:625- 630.

12. Hu Z, Ou L, Li S, Yang L. Synthesis and biological evaluation of 1-cyano2-amino-benzimidazole derivatives as a novel class of antitumor agents. Med Chem Res. 2014;23:3029-3038.

13. Demirel S, Ayhan Kilcigil G, Kara Z, Guven B, Onay Besikci A. Synthesis and pharmacologic evaluation of some benzimidazole acetohydrazide derivatives as EGFR inhibitors. Turk J Pharm Sci. 2017;14:285-289.

14. Jawaid AM, Anees AS, Ahsan AK, Zulphikar A. Design, synthesis, docking and QSAR study of substituted benzimidazole linked oxadiazole as cytotoxic agents. Eur J Med Chem. 2017;126:853-869.

15. Cheong JF, Zaffagni M, Chung I, Xu Y, Wang Y, Jernigan FE, Zetter BR, Sun L. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. Eur J Med Chem. 2018;144:372-385.

16. Nakano H, Inoue T, Kawasaki N, Miyataka H, Matsumoto H, Taguchi T, Inagaki N, Nagai H, Satoh T. Synthesis and biological activities of novel antiallergic agents 5-lipoxygenase ınhibiting action. Bioorg Med Chem. 2000;8:373-380.

17. Can Eke B, Puskullu MO, Buyukbingol E, Iscan M. Study on the antioxidant capacities of some benzimidazoles in rat tissues. Chem Biol Interact. 1998;113:65-77.

18. Ayhan-Kilcigil G, Kus C, Coban T, Can-Eke B, Iscan M. Synthesis and anti-oxidant properties of novel benzimidazole Derivatives. J Enzym Inhib Med Chem. 2004;19:129-135.

19. Ayhan-Kilcigil G, Kus C, Coban T, Can-Eke B, Ozbey SM. Iscan. Synthesis, Antioxidant and Radical Scavenging Activities of Novel Benzimidazoles. J Enzym Inhib Med Chem. 2005;20:503-514.

20. Ayhan-Kilcigil G, Kus C, Ozdamar ED, Can-Eke B, Iscan M. Synthesis and antioxidant capacities of some new benzimidazole derivatives. Arch Pharm. 2007;340:607-611.

21. Ayhan-Kilcigil G, Gurkan S, Coban T, Ozdamar ED, Can-Eke B. Synthesis and evaluation of antioxidant properties of novel 2-[2-(4-chlorophenyl) benzimi-dazole-1-yl]-n-(2-arylmethylene amino) acetamides and 2-[2-(4-chlorophenyl) benzimidazole-1-yl]-n-(4-oxo-2-arylthiazolidine-3-yl) acetamides-I. Chem Bio Drug Des. 2012;79:869-877.

22. Ayhan-Kilcigil G, Kus C, Coban T, Can-Eke B, Ozdamar ED, Can-Eke B. Identification of a novel series of n-phenyl-5-[(2-phenylbenzimidazol-1- yl)methyl]-1,3,4-oxadiazol-2-amines as potent antioxidants and radical scavengers. Arch Pharm. 2014;347:276-282.

23. Kus C, Ayhan-Kilcigil G, Can-Eke B, Iscan M. Synthesis and antioxidant properties of some novel benzimidazole derivatives on lipid peroxidation in the rat liver. Arch Pharm Res. 2004;27:156-163.

24. Kus C, Ayhan-Kilcigil G, Ozbey S, Kaynak FB, Kaya M, Coban T, CanEke B. Synthesis and antioxidant properties of novel n-methyl-1,3,4- thiadiazol-2-amine and 4-methyl-2h-1,2,4-triazole-3(4h)-thione derivatives of benzimidazole class. Bio Med Chem. 2008;16:4294-4303.

25. Kerimov I, Ayhan-Kilcigil G, Can-Eke B, Altanlar N, Iscan M. Synthesis, antifungal and antioxidant screening of some novel benzimidazole derivatives. J Enzym Inhib Med Chem. 2007;22:696-701.

26. Kerimov I, Ayhan-Kilcigil G, Ozdamar ED, Can-Eke B, Coban T, Ozbey S, Kazak C. Design and one-pot and microwave-assisted synthesis of 2-amino/5-aryl-1,3,4-oxadiazoles bearing a benzimidazole moiety as antioxidants. Arch Pharm. 2012;3457:549-556.

27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJJ. Protein measurement with the Folin phenol reagent. Biol Chem. 1951;193:265-275.

28. Iscan M, Arinc E, Vural N, Iscan MY. In vivo effects of 3-methylcholantrene, phenobarbital, pyretrum and 2.4.5-T isooctylester on liver, lung and kidney microsomal mixed-function oxidase system of guinea-pig: a comparative study. Comp Biochem Physiol. 1984;77:77-190.

29. Wills ED. Mechanisms of lipid peroxide formation in animal tissues. Biochem J. 1966;99:667-676.

30. Wills ED. Lipid peroxide formation in microsomes. Relationship of hydroxylation to lipid peroxide formation. Biochem J. 1969;113:333-341.

31. Bishayee S, Balasubramanian AS. Lipid peroxide formation in rat brain. J Neurochem. 1971;18:909-920.

32. Burke MD, Thompson S, Elcombe CR, Halpert J, Haaparanta T, Mayer RT. Ethoxy-, pentoxy- and benzyloxyphenoxazones and homologues: a series of substrates to distinguish between different induced cytochromes P-450. Biochem Pharmacol. 1985;34:3337-3345.

33. Alp AS, Kilcigil GA, Ozdamar ED, Coban T, Eke B. Synthesis and evaluation of antioxidant activities of novel 1,3,4-oxadiazole and imine containing 1H-benzimidazoles. Turk J Chem. 2015;39:42-53.

___

Turkish Journal of Pharmaceutical Sciences
  • ISSN: 1304-530X
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 2000

6.6b293

Sayıdaki Diğer Makaleler

Combined Effects of Protocatechuic Acid and 5-Fluorouracil on p53 Gene Expression and Apoptosis in Gastric Adenocarcinoma Cells

Zahra MOTAMED, Sayed Asadollah AMINI, Elham RAEISI, Yves LEMOIGNE, Esfandiar HEIDARIAN

In Situ Absorption Study of Acebutolol by Modulating P-glycoprotein with Verapamil in Rats

ssam Mohammed ABUSHAMMALA, Elham Abed ABUWAKED, Hanan Mohammed FAYYAD, Ahmed Fadel ELQEDRA, Mai Abed Alrahman RAMADAN, Ihab Mustafa ALMASRI

Development of a New Approach for Standardization of the Herb Centaurium erythraea Rafn. by High Performance Liquid Chromatography

Svitlana M. GUBAR, Anna S. MATERIIENKO, Nataliia M. SMIELOVA, Liana G. BUDANOVA, Victoriya A. GEORGIYANTS

New Therapeutic Approaches in Cystic Fibrosis

Dolunay Merve FAKIOĞLU, Beril ALTUN

An Investigation on the In Vitro Wound Healing Activity and Phytochemical Composition of Hypericum pseudolaeve N. Robson Growing in Turkey

Bahar İĞCİ, Zeki AYTAÇ

A Novel Genotyping Method for Detection of the Muscarinic Receptor M1 Gene rs2067477 Polymorphism and Its Genotype/Allele Frequencies in a Turkish Population

Fezile ÖZDEMİR, Yağmur KIR, Kenan Can Tok, Bora BASKAK, Halit Sinan SÜZEN

4Federal University Dutsin-Ma, Department of Applied Chemistry, Dutsin-Ma, Katsina State, Nigeria

Oluwasesan M. BELLO, Olubunmi Stephen OGUNTOYE, Adewumi Oluwasogo DADA, Oluwatoyin E. BELLO, Tiijani ALİ

Antifungal and Antibiofilm Activities of Selective Serotonin Reuptake Inhibitors Alone and in Combination with Fluconazole

YAMAÇ TEKİNTAŞ, AYBALA TEMEL, Ayşegül ATEŞ, Bayrı ERAÇ, Dilek Yeşim METİN, Süleyha Hilmioğlu POLAT, Mine HOŞGÖR LİMONCU

Can Alpha-1 Antitrypsin Levels be Used to Predict the Prognosis of COVID-19 Therapy?

Elif ARAS, Nesligül ÖZDEMİR, Kutay DEMİRKAN

Effects of Polyvinylpyrrolidone and Ethyl Cellulose in Polyurethane Electrospun Nanofibers on Morphology and Drug Release Characteristics

Aslı GENÇTÜRK, Emine KAHRAMAN, SEVGİ GÜNGÖR, Yıldız ÖZSOY, A. Sezai SARAÇ