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Synthesis and Biological Evaluation of Some New Benzimidazole Derivatives Bearing Dithiocarbamate Moiety as Potential Cholinesterase Inhibitors

Year 2014, Volume: 39 Issue: 4, 0 - , 22.07.2014
https://doi.org/10.17826/cutf.79473

Abstract

Purpose: The synthesis of eight new benzimidazole derivatives bearing dithiocarbamate moiety and subsequently their anticholinesterase activity evaluations were aimed in this present study. Material and Method: 2-Bromoacetylbenzimidazole react with dithiocarbamate salt derivatives and the resulted compounds were elucidated by 1H NMR, mass spectral data, and elemental analyses. Each derivative was evaluated for its ability to inhibit acetylcholinesterase (AChE) in vitro by using a modification of Ellman"s spectrophotometric method. Results: The new compound 1-methyl-2{2"[(N,Ndimethylaminothiocarbamoylthio)-acetyl]}benzimidazole (2b) can be identified as promising anticholinesterase agent in vitro due to its moderate inhibition effect, which is about 37%, when compared with standard substance Donepezil under the same experimental conditions. Conclusion: In comparing with the reference standard, among the synthesized eight new compounds the only compound namely 1-methyl-2{2"[(N,Ndimethylaminothiocarbamoyl-thio)-acetyl]}benzimidazole (2b) has a promising anticholinesterase activity.

References

  • Racchi M, Mazzucchelli M, Porello E, Lanni C, Govoni S, Acetylcholinesterase inhibitors: novel activities of old molecules, Pharmacological Research. 2004;21:441-51.
  • Kosasa T, Kuriya Y, Matsui K, Yamanishi Y, Inhibitory effects of donepezil hydrochloride (E2020) on cholinesterase activity in brain and peripheral tissues of young and aged rats, European Journal of Pharmacology. 1999;386:7-13.
  • Carreiras MC, Marco Jl, Recent approaches to novel anti-alzheimer therapy, Current Pharmaceutical Design. 2004;25:3167-75.
  • Parihar MS, Hemnani T, Alzheimer’s disease pathogenesis and therapeutic interventions, Journal of Clinical Neuroscience. 2004;11:456-67.
  • Thacker PD, Surprising discovery with Alzheimer’s medication, Drug Discovery Today. 2003;1:8- 9
  • Tabet N, Acetylcholinesterase inhibitors for Alzheimer’s disease, anti-inflammatories in acetylcholine clothing, Age and Aging. 2006;35:336
  • Giacobini E, Spiegel R, Enz A, Veroff AE, Cutler NR, Inhibition of acetyl- and butryl-cholinesterase in the serebrospinal fluid of patients with Alzheimer’s disease by rivastigmine: correlation with cognitive benefit, Journal of Neural Transmission. 2002;109:1053-65.
  • Standridge JB, Pharmacotherapeutic Approaches to the treatment of Alzheimer's Disease, Clin. Ther. 2004;26:615–30.
  • Lemke TL, Williams DA, Foye’s Principles of Medicinal Chemistry. Lippincott Williams & Wilkins, Baltimore. 2008.
  • Wilkinson DG, Francis PT, Schwam E, PayneParrish J, Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy, Drugs Aging. 2004;21:453–78.
  • Pepeu G, Giovannini MG, Cholinesterase inhibitors and beyond, Curr, Alzheimer Res. 2009;6:86–96.
  • Grutzendler J, Morris JC, Cholinesterase inhibitors for Alzheimer's disease, Drugs. 2001;61:41–52.
  • Martinez A, Castro A, Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease. Expert Opin. Investig, Drugs. 2006;15:1–12.
  • Johannsen P, Long-Term Cholinesterase Inhibitor Treatment of Alzheimer’s Disease, CNS Drugs .2004;18:757–68.
  • Shen ZX, Brain cholinesterases: III. Future perspectives of AD research and clinical practice Med, Hypotheses. 2004;63:298–307.
  • Giacobini E, Emerging Drugs and Targets for Alzheimer's Disease, Neurochem. Res. 2003; 28: 515–22.
  • Turan-Zitouni G, Ozdemir A, Guven K, Synthesis of Some 1-[(N,N-Disubstituted thiocarbamoylthio)acetyl]-3-(2-thienyl)-5-aryl-2pyrazoline Derivatives and Investigation of Their Antibacterial and Antifungal Activities, Arch Pharm Chem Life Sci. 2005;338:96–104.
  • Tokuyama R, Takahashi Y, Tomita Y, Tsubouchi M, Yoshida T, Iwasaki N, Kado N, Okezaki E, Nagata O, Structure–Activity Relationship (SAR) Studies on OxazolidinoneAntibacterial Agents. 2.1) Relationship between Lipophilicity and Antibacterial Activity in 5Thiocarbonyl Oxazolidinones,Chem Pharm Bull. 2001;49: 353–60.
  • Wang XJ, Xu HW, Guo LL. Zheng JX, Xu JX, Guo CX. Design and synthesis of novel 1,2,3-triazoledithiocarbamate hybrids as potential anticancer agents, Bioorg Med ChemLett. 2011;21:3074–77.
  • Patani GA, LaVoie EJ, Chemical Similarity and Biological Activities, Chem Rev. 1996;96:3147–76.
  • Waterbeemd H, Mannhold R, In Lipophilicity Descriptors for Structure Property Correlation Studies: Overview of Experimental and Theoretical Methods and a Benchmark of Log P Calculations, Lipophilicity in Drug Action and Toxicology. (R. Mannhold, H. Kubinyi, H. Timmerman, Series, Eds., V. Pliska, B. Testa, H. Waterbeemd Vol, Eds.), VCH Publishers, New York, USA 1996, chapter 23.
  • Bacharaju K, Jambula SR, Sivan S, Jyostnatangeda S, Manga V, Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents. Bioorg Med Chem Lett. 2012;22:3274-77.
  • Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, Osman H, Masand VH, Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors, Bioorg Chem. 2013;49:33-9.
  • Alpan AS, Parlar S, Carlino L, Tarikogullari AH, Alptüzün V, Synthesis, biological activity and molecular modeling studies on 1H-benzimidazole derivatives as acetylcholinesterase inhibitors.Bioorg Med Chem. 2013;21:4928–37.
  • Yoon YK, Ali MA, Wei AC, Choon TS, Kumar RS, Drug Design: An Efficient and Facile Synthesis of Novel Polar Benzimidazoles of Biological Interests, Drug Des. 2013;3:110.
  • Karali N, Apak, I, Ozkirimli S, Gursoy A, Dogan SU, Eraslan A, Ozdemir O, Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine, Arch. Pharm Med Chem. 1999;332:422-6.
  • Perry NSL, Houghton PJ, Theobald AE, Jenner P, Perry EK. In-vitro inhibition of human erythrocyte acetylcholine esterase by Salvia lavandulae folia essential oil and constituent terpenes, J Pharm Pharmacol. 2000;52:895-902.
  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem Pharmacol. 1961;7:88-95 .
  • Yazışma Adresi / Address for Correspondence: Dr.Usama Abu Mohsen Faculty of Pharmacy, Al-Azhar University, Department of Pharmaceutical Chemistry, Gaza, PALESTINE E-mail: usamapharmacy@gmail.com G eliş tarihi/Received on :21.03.2014
  • Kabul tarihi/Accepted on: 25.04.2014

Ditiyiokarbamat Yapısı İçeren Yeni Bazı Benzimidazol Türevlerinin Sentezi ve Potansiyel Kolinesteraz İnhibitörleri olarak Biyolojik Etki Çalışmaları

Year 2014, Volume: 39 Issue: 4, 0 - , 22.07.2014
https://doi.org/10.17826/cutf.79473

Abstract

Amaç: Bu çalışmada, ditiyokarbamat yapısı içeren benzimidazol türevlerinden sekiz yeni madde sentezlenmiş olup, in vitro koşullarda antikolinesteraz aktivitelerinin değerlendirilmesi amaçlanmıştır. Materyal ve Metod: 2-Bromoasetilbenzimidazol ve ditiyokarbamat türevlerinin reaksiyonu sonucu sentezlenen bileşiklerin yapıları 1H-NMR, kütle spektral verileri ayrıca elemental analiz ile aydınlatılmıştır. Ayrıca yapıları tayin edilmiş bileşiklerin Elmann"s spektrofotometrik yöntemiyle asetilkolin esteraz etkileri değerlendirilmiştir. Bulgular: Tüm bileşikler arasında 1-metil-2{2"[N,Ndimetilaminokarbamoyl-tio)asetil]}benzimidazol (2b) maddesi kayda değer in vitro antikolinesteraz aktivite göstermiştir. Referans madde olarak kullanılan Donepezil ile aynı koşullarda kıyaslandığında, 2b maddesi %37 oranında inhibe ettiği görülmüştür. Sonuç: Sentezlenen sekiz yeni bileşikten sadece (1-metil-2{2"[N,Ndimetilaminokarbamoyl-tio)asetil]}benzimidazol (2b) maddesi Donepezil ile kıyaslandığında, kayda değer in vitro antikolinesteraz aktiviteye sahip olduğu tespit edilmiştir.

References

  • Racchi M, Mazzucchelli M, Porello E, Lanni C, Govoni S, Acetylcholinesterase inhibitors: novel activities of old molecules, Pharmacological Research. 2004;21:441-51.
  • Kosasa T, Kuriya Y, Matsui K, Yamanishi Y, Inhibitory effects of donepezil hydrochloride (E2020) on cholinesterase activity in brain and peripheral tissues of young and aged rats, European Journal of Pharmacology. 1999;386:7-13.
  • Carreiras MC, Marco Jl, Recent approaches to novel anti-alzheimer therapy, Current Pharmaceutical Design. 2004;25:3167-75.
  • Parihar MS, Hemnani T, Alzheimer’s disease pathogenesis and therapeutic interventions, Journal of Clinical Neuroscience. 2004;11:456-67.
  • Thacker PD, Surprising discovery with Alzheimer’s medication, Drug Discovery Today. 2003;1:8- 9
  • Tabet N, Acetylcholinesterase inhibitors for Alzheimer’s disease, anti-inflammatories in acetylcholine clothing, Age and Aging. 2006;35:336
  • Giacobini E, Spiegel R, Enz A, Veroff AE, Cutler NR, Inhibition of acetyl- and butryl-cholinesterase in the serebrospinal fluid of patients with Alzheimer’s disease by rivastigmine: correlation with cognitive benefit, Journal of Neural Transmission. 2002;109:1053-65.
  • Standridge JB, Pharmacotherapeutic Approaches to the treatment of Alzheimer's Disease, Clin. Ther. 2004;26:615–30.
  • Lemke TL, Williams DA, Foye’s Principles of Medicinal Chemistry. Lippincott Williams & Wilkins, Baltimore. 2008.
  • Wilkinson DG, Francis PT, Schwam E, PayneParrish J, Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy, Drugs Aging. 2004;21:453–78.
  • Pepeu G, Giovannini MG, Cholinesterase inhibitors and beyond, Curr, Alzheimer Res. 2009;6:86–96.
  • Grutzendler J, Morris JC, Cholinesterase inhibitors for Alzheimer's disease, Drugs. 2001;61:41–52.
  • Martinez A, Castro A, Novel cholinesterase inhibitors as future effective drugs for the treatment of Alzheimer's disease. Expert Opin. Investig, Drugs. 2006;15:1–12.
  • Johannsen P, Long-Term Cholinesterase Inhibitor Treatment of Alzheimer’s Disease, CNS Drugs .2004;18:757–68.
  • Shen ZX, Brain cholinesterases: III. Future perspectives of AD research and clinical practice Med, Hypotheses. 2004;63:298–307.
  • Giacobini E, Emerging Drugs and Targets for Alzheimer's Disease, Neurochem. Res. 2003; 28: 515–22.
  • Turan-Zitouni G, Ozdemir A, Guven K, Synthesis of Some 1-[(N,N-Disubstituted thiocarbamoylthio)acetyl]-3-(2-thienyl)-5-aryl-2pyrazoline Derivatives and Investigation of Their Antibacterial and Antifungal Activities, Arch Pharm Chem Life Sci. 2005;338:96–104.
  • Tokuyama R, Takahashi Y, Tomita Y, Tsubouchi M, Yoshida T, Iwasaki N, Kado N, Okezaki E, Nagata O, Structure–Activity Relationship (SAR) Studies on OxazolidinoneAntibacterial Agents. 2.1) Relationship between Lipophilicity and Antibacterial Activity in 5Thiocarbonyl Oxazolidinones,Chem Pharm Bull. 2001;49: 353–60.
  • Wang XJ, Xu HW, Guo LL. Zheng JX, Xu JX, Guo CX. Design and synthesis of novel 1,2,3-triazoledithiocarbamate hybrids as potential anticancer agents, Bioorg Med ChemLett. 2011;21:3074–77.
  • Patani GA, LaVoie EJ, Chemical Similarity and Biological Activities, Chem Rev. 1996;96:3147–76.
  • Waterbeemd H, Mannhold R, In Lipophilicity Descriptors for Structure Property Correlation Studies: Overview of Experimental and Theoretical Methods and a Benchmark of Log P Calculations, Lipophilicity in Drug Action and Toxicology. (R. Mannhold, H. Kubinyi, H. Timmerman, Series, Eds., V. Pliska, B. Testa, H. Waterbeemd Vol, Eds.), VCH Publishers, New York, USA 1996, chapter 23.
  • Bacharaju K, Jambula SR, Sivan S, Jyostnatangeda S, Manga V, Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents. Bioorg Med Chem Lett. 2012;22:3274-77.
  • Yoon YK, Ali MA, Wei AC, Choon TS, Khaw KY, Murugaiyah V, Osman H, Masand VH, Synthesis, characterization, and molecular docking analysis of novel benzimidazole derivatives as cholinesterase inhibitors, Bioorg Chem. 2013;49:33-9.
  • Alpan AS, Parlar S, Carlino L, Tarikogullari AH, Alptüzün V, Synthesis, biological activity and molecular modeling studies on 1H-benzimidazole derivatives as acetylcholinesterase inhibitors.Bioorg Med Chem. 2013;21:4928–37.
  • Yoon YK, Ali MA, Wei AC, Choon TS, Kumar RS, Drug Design: An Efficient and Facile Synthesis of Novel Polar Benzimidazoles of Biological Interests, Drug Des. 2013;3:110.
  • Karali N, Apak, I, Ozkirimli S, Gursoy A, Dogan SU, Eraslan A, Ozdemir O, Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine, Arch. Pharm Med Chem. 1999;332:422-6.
  • Perry NSL, Houghton PJ, Theobald AE, Jenner P, Perry EK. In-vitro inhibition of human erythrocyte acetylcholine esterase by Salvia lavandulae folia essential oil and constituent terpenes, J Pharm Pharmacol. 2000;52:895-902.
  • Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity, Biochem Pharmacol. 1961;7:88-95 .
  • Yazışma Adresi / Address for Correspondence: Dr.Usama Abu Mohsen Faculty of Pharmacy, Al-Azhar University, Department of Pharmaceutical Chemistry, Gaza, PALESTINE E-mail: usamapharmacy@gmail.com G eliş tarihi/Received on :21.03.2014
  • Kabul tarihi/Accepted on: 25.04.2014
There are 30 citations in total.

Details

Primary Language Turkish
Journal Section Research
Authors

Usama Abu Mohsen This is me

Publication Date July 22, 2014
Published in Issue Year 2014 Volume: 39 Issue: 4

Cite

MLA Mohsen, Usama Abu. “Ditiyiokarbamat Yapısı İçeren Yeni Bazı Benzimidazol Türevlerinin Sentezi Ve Potansiyel Kolinesteraz İnhibitörleri Olarak Biyolojik Etki Çalışmaları”. Cukurova Medical Journal, vol. 39, no. 4, 2014, doi:10.17826/cutf.79473.