×
Home Current Archive Editorial board
News Contact
Research paper

In vitro assessment of the lipid peroxidation of N,N'-disubstituted benzimidazole-2-thiones: Hydrazides vs esters

By
Jelena Lazarević Orcid logo ,
Jelena Lazarević
Jelena Zvezdanović Orcid logo ,
Jelena Zvezdanović
Neda Anastassova ,
Neda Anastassova
Anelia Mavrova ,
Anelia Mavrova
Denitsa Yancheva ,
Denitsa Yancheva
Andrija Šmelcerović Orcid logo
Andrija Šmelcerović

Abstract

Introduction: Oxidative stress and resulting lipid peroxidation are involved in numerous pathological conditions. For this reason, the role of antioxidants attracts attention and the radical-scavenging capacity of many natural and synthetic supplements and drugs has been extensively evaluated. Material and methods: In the present study, seven N,N'-disubstituted benzimidazole-2-thiones with ester (1 - 4) and hydrazide (5 - 7) side chains were investigated for in vitro antioxidant activity using lipid peroxidation method. Results: Among the assayed compounds, three hydrazides, 1,3-bis[3-(hydrazinooxy)-3-oxopropyl]-1,3dihydro-2H-benzimidazole-2-thione (5), 1,3-bis[3-(hydrazinooxy)-3-oxopropyl]-5-methyl-1,3-dihydro-2H benzimidazole-2-thione (6) and 1,3-bis[3-(hydrazinooxy)-3-oxopropyl]-5-benzoyl-1,3-dihydro-2H benzimidazole-2-thione (7) showed good antioxidant properties (IC50 ˂ 100 mM), with the best lipid peroxidation inhibition values (IC50) shown for compound 5 (64 ± 10 mM) and compound 6 (73 ± 29 mM). Conclusion: Indicated hydrazide structures may constitute a sort of molecular basis, a promising starting point for the development of compounds for the prevention and treatment of diseases resulting from oxidative damage.

References

1.
Johns JR, Platts JA. Theoretical insight into the antioxidant properties of melatonin and derivatives. Org Biomol Chem. 12(39):7820–7.
2.
Galano A, Tan DX, Reiter RJ. Melatonin as a natural ally against oxidative stress: a physicochemical examination. Journal of Pineal Research. 2011;51(1):1–16.
3.
Karadag A, Ozcelik B, Saner S. Review of Methods to Determine Antioxidant Capacities. Food Analytical Methods. 2009;2(1):41–60.
4.
Lazarević J, Šmelcerović A, Zvezdanović J, Yancheva D, Casati S, Ottria R, et al. Lipid peroxidation inhibition study: A promising case of 1,3-di([1,1′-biphenyl]-3-yl)urea. Chemico-Biological Interactions. 2020;326:109137.
5.
Kolarević A, Ilić BS, Anastassova N, Mavrova ATs, Yancheva D, Kocić G, et al. Benzimidazoles as novel deoxyribonuclease I inhibitors. Journal of Cellular Biochemistry. 2018;119(11):8937–48.
6.
Elkamhawy A, Woo J, Gouda NA, Kim J, Nada H, Roh EJ, et al. Melatonin Analogues Potently Inhibit MAO-B and Protect PC12 Cells against Oxidative Stress. Antioxidants. 10(10):1604.
7.
Reina M, Castañeda-Arriaga R, Perez-Gonzalez A, Guzman-Lopez EG, Tan DX, Reiter RJ, et al. A Computer-Assisted Systematic Search for Melatonin Derivatives with High Potential as Antioxidants. Melatonin Research. 1(1):27–58.
8.
Anastassova NO, Mavrova ATs, Yancheva DY, Kondeva-Burdina MS, Tzankova VI, Stoyanov SS, et al. Hepatotoxicity and antioxidant activity of some new N,N′-disubstituted benzimidazole-2-thiones, radical scavenging mechanism and structure-activity relationship. Arabian Journal of Chemistry. 2018;11(3):353–69.
9.
Suzen S. Melatonin and Synthetic Analogs as Antioxidants. Current Drug Delivery. 2013;10(1):71–5.
10.
Beckhauser TF, Francis-Oliveira J, De Pasquale R. Reactive Oxygen Species: Physiological and Physiopathological Effects on Synaptic Plasticity. Journal of Experimental Neuroscience. 2016;10s1.
11.
Shirinzadeh H, Eren B, Gurer-Orhan H, Suzen S, Özden S. Novel Indole-Based Analogs of Melatonin: Synthesis and in Vitro Antioxidant Activity Studies. Molecules. 15(4):2187–202.
12.
Mavrova ATs, Yancheva D, Anastassova N, Anichina K, Zvezdanovic J, Djordjevic A, et al. Synthesis, electronic properties, antioxidant and antibacterial activity of some new benzimidazoles. Bioorganic & Medicinal Chemistry. 2015;23(19):6317–26.
13.
Kuş C, Ayhan-Kılcıgil G, Özbey S, Kaynak FB, Kaya M, Çoban T, et al. 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. Bioorganic & Medicinal Chemistry. 2008;16(8):4294–303.
14.
GURER-ORHAN H, ORHAN H, SUZEN S, ORHAN PÜSKÜLLÜ M, BUYUKBINGOL E. Synthesis and evaluation ofin vitroantioxidant capacities of some benzimidazole derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry. 2006;21(2):241–7.
15.
Salahuddin, Shaharyar M, Mazumder A. Benzimidazoles: A biologically active compounds. Arabian Journal of Chemistry. 2017;10:S157–73.
16.
Ramana KV, Srivastava S, Singhal SS. Lipid Peroxidation Products in Human Health and Disease 2016. Oxidative Medicine and Cellular Longevity. 2017;2017(1).
17.
Collin F. Chemical Basis of Reactive Oxygen Species Reactivity and Involvement in Neurodegenerative Diseases. International Journal of Molecular Sciences. 20(10):2407.

Citation

Article metrics

Google scholar: See link

The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.