Araştırma Makalesi
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Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi

Yıl 2019, Cilt: 21 Sayı: 1, 94 - 105, 15.03.2019
https://doi.org/10.25092/baunfbed.522970

Öz

Birçok antimikrobik maddeye karşı direnç geliştirmiş mikroorganizmaların oluşturduğu toplumsal ve hastane kaynaklı enfeksiyonlar büyük bir sorun oluşturmaktadır ve bu enfeksiyonların tedavisinde yeni ajanların kullanımı ile sağaltımın etkili olması sağlanabilmektedir. Bu çalışmada yapısal farklılıklar içeren bazı benzimidazol türevlerinin antimikrobiyal etkileri mikrodilüsyon ve disk diffüsyon tekniklerini kullanarak incelenmiştir. Çalışılan bileşikler içerdikleri benzimidazol birimi sayısı, benzimidazol halkasının 1 ve 5 konumunda farklı sübstitüsyonu, 2-fenilbenzimidazol yapısının p- konumunda farklı sübstitüsyonu ve aromatik birimler içerip içermemeleri gibi yönlerden farklılıklar içermektedir. Bu yolla amaca uygun yeni benzimidazollerin sentezi için literatüre yapı-aktivite ilişkilerine dair önemli bilgilerin kazandırılması hedeflenmiştir. İncelenmek üzere, klinikte önem taşıyan ve direnç oluşumu açısından da önemli olan Gram + ve Gram –bakterileri içeren klinik tip türleri seçilmiştir. Benzimidazol türevi maddelerin etkileri standart antimikrobik ajanlarla kıyaslanmıştır. Benzimidazol halkasının sayısına bağlı olarak antimikrobiyal etkinin arttığı, benzimidazole 2- konumunda bağlı tiyofen ve piridin gibi hetero halkalı grupların aktiviteyi arttırdığı, 5-Cl sübstitüsyonunun benzimidazole tüm bakteri türlerine karşı etkili olma özelliği kazandırdığı belirlenmiştir. Ayrıca, 2-fenil benzimidazolün p- konumunda elektron çekici Cl ve NO2, içeren türevlerin elektron verici OCH3 ve CH3 içeren türevlere göre bakteri türlerine karşı daha etkin olduğu tespit edilmiştir.

Kaynakça

  • Darcan, C., Kaygusuz, Ö. ve Korkmaz, T., Antimicrobial effectiveness of [Cu(pzdc)(phen)2]·5.5H2O complex on some microorganisms, Journal of Pure and Applied Microbiology, 7, 4, 2747-2756, (2013).
  • Kaye, K.S., Engemann, J.J., Fraimow, H.S. ve Abrutyn, E, Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms, and clinical management, Infectious Disease Clinics of North America, 18, 467-11, (2004).
  • Kumar, D., Jacob, M.R., Reynolds, M.B. ve Kerwin, S.M., Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1, Bioorganic&Medcinal Chemistry, 10, 12, 3997-4004, (2002).
  • El Rashedy, A. A. ve Aboul-Enein, H. Y, Benzimidazole derivates as potential chemotherapeutic agents, Current Drug Therapy, 8, 1-14, (2013).
  • Aboul-Enein, H.Y. ve El Rashedy, A.A., Benzimidazole Derivatives as Antidiabetic Agents, Medicinal chemistry, 5, 7, 318-325, (2015).
  • Bansal, Y. ve Silakari, O., The therapeutic journey of benzimidazoles: A review, Bioorganic& Medicinal Chemistry, 20, 21, 6208-36, (2012) .
  • Salahuddin, Shaharyar, M. ve Mazumder, A., Benzimidazoles: A biologically active compounds, Arabian Journal of Chemistry, 10, 157–173, (2017).
  • Sharma, P., Rane, N. ve Gurram, V.K., Synthesis and QSAR studies of pyrimido [4, 5-d] pyrimidine- 2, 5-dione derivatives as potential antimicrobial agents. Bioorganic & Medicinal Chemistry Letters, 14, 4185–4190, (2004).
  • Sharma, S., Gangal, S. ve Rauf, A., Convenient one-pot synthesis of novel 2-substituted benzimidazoles, tetrahydrobenzimidazoles and imidazoles and evaluation of their in vitro antibacterial and antifungal activities, European Journal of Medicinal Chemistry, 44, 1751-1757, (2009).
  • Eren, B. ve Bekdemir, Y., Simple, mild and highly efficient synthesis of 2-substituted benzimidazoles and bisbenzimidazoles, Quimica Nova, 37, 4, 643-647, (2014).
  • Eren, B. ve Unal, A., Molecular structure and spectroscopic analysis of 1,4-Bis(1-methyl-2-benzimidazolyl)benzene; XRD, FT-IR, dispersive-Raman, NMR and DFT studies, Spectrochimica Acta Part A, 103, 222–231, (2013).
  • NCCLS Standarts. Clinical and Laboratory Standards Institute, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th edition, CLSI document M7-A7, Clinical Laboratory Standards Institute, Wayne, PA, (2007).
  • Wiegand, I., Hilpert, K. ve Hancock, R. E. W., Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protocols, 3, 163−175 (2008).
  • Sarker, S. D., Nahar, L. ve Kumarasamy, Y., Microtitre platebased antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals, Methods, 42, 321−324 (2007).
  • Isik, K. ve Özdemir-Kocak, F., Antimicrobial activity screening of some sulfonamide derivatives on some Nocardia species and isolates, Microbiological Research, 164, 49−58 (2009).
  • Gülay, Z., Antibiyotik duyarlılık testlerinin yorumu, Toraks Dergisi, 3,1, 75-88, (2002).
  • Abdel Ghani, N.T. ve Mansour, A. M., Novel Pd(II) and Pt(II) complexes of N,N-donor benzimidazole ligand: Synthesis, spectral, electrochemical, DFT studies and evaluation of biological activity, Inorganica Chimica Acta, 373, 249–258, (2011).
  • Unal, A. ve Eren, B., FT-IR, dispersive Raman, NMR, DFT and antimicrobial activity studies on 2-(Thiophen-2-yl)-1H-benzo[d]imidazole, Spectrochimica Acta Part A, 114, 129–136, (2013).
  • Kenchappa, R., Bodke, Y.D., Telkar, S. ve M. Aruna, S., Antifungal and anthelmintic activity of novel benzofuran derivatives containing thiazolo benzimidazole nucleus: an in vitro evaluation, Journal of Chemical Biology, 10, 11–23, (2017).
  • Sharma , M. C., Structural insight for (6-oxo-3-pyridazinyl)-benzimidazoles derivatives as angiotensin II receptor antagonists: QSAR, pharmacophore identification and kNNMFA approach, Journal of Saudi Chemical Society, 19,3, 265-273, (2012).
  • Sharma, D., Narasimhan, B., Kumar, P. ve Jalbout, A., Synthesis and QSAR evaluation of 2-(substituted phenyl)-1Hbenzimidazoles and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones, European Journal of Medicinal Chemistry, 44, 1119-1127, (2009).
  • Abdel Ghani, N.T. ve Mansour, A. M., Novel Ni(II) and Zn(II) complexes coordinated by 2-arylaminomethyl-1Hbenzimidazole: Molecular structures, spectral, DFT studies and evaluation of biological activity, Inorganica Chimica Acta, 104, 134-142, (2013).

Detailed examination of structural factors effecting antimicrobial activity of benzimidazole ring by disk diffusion and microdilution method

Yıl 2019, Cilt: 21 Sayı: 1, 94 - 105, 15.03.2019
https://doi.org/10.25092/baunfbed.522970

Öz

Socio-and hospital-acquired infections caused by microorganisms that have developed resistance to many antimicrobial agents constitute a major problem, and the use of new agents in the treatment of these infections can make treatment effective. In this study, antimicrobial effects of different benzimidazole derivatives were investigated using microdilution and disc diffusion techniques. The compounds studied include differences in the number of benzimidazole units they contain, the different substitutions of the benzimidazole ring in positions 1 and 5, the different substitution of the 2-phenyl benzimidazole structure in the p- position, and the presence or absence of aromatic units. In this way, it is aimed to gain important knowledge to the literature about structure-activity relations for the synthesis of novel benzimidoles which are suitable for the purpose. To examine, clinical types including Gram +and Gram –bacteria , which are clinically important and important for resistance formation, have been selected. The activity of benzimidazole derivatives was compared with standard antimicrobial agents. Results indicated that antimicrobial activity increases proportionally with the number of benzimidazole rings, heterocyclic groups such as thiophene and pyridine connected to benzimidazole at position 2- increases the activity, 5-Cl substituion get benzimidazole to be active against  all bacterial species. Also, it was determined that the derivates having electron withdrawing Cl and NO2 sübstitüents at the p- position of 2-phenyl benzimidazole are more effective than the derivates having electron donating OCH3 ve CH3 sübstitüents  against bacterial strains.

Kaynakça

  • Darcan, C., Kaygusuz, Ö. ve Korkmaz, T., Antimicrobial effectiveness of [Cu(pzdc)(phen)2]·5.5H2O complex on some microorganisms, Journal of Pure and Applied Microbiology, 7, 4, 2747-2756, (2013).
  • Kaye, K.S., Engemann, J.J., Fraimow, H.S. ve Abrutyn, E, Pathogens resistant to antimicrobial agents: epidemiology, molecular mechanisms, and clinical management, Infectious Disease Clinics of North America, 18, 467-11, (2004).
  • Kumar, D., Jacob, M.R., Reynolds, M.B. ve Kerwin, S.M., Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1, Bioorganic&Medcinal Chemistry, 10, 12, 3997-4004, (2002).
  • El Rashedy, A. A. ve Aboul-Enein, H. Y, Benzimidazole derivates as potential chemotherapeutic agents, Current Drug Therapy, 8, 1-14, (2013).
  • Aboul-Enein, H.Y. ve El Rashedy, A.A., Benzimidazole Derivatives as Antidiabetic Agents, Medicinal chemistry, 5, 7, 318-325, (2015).
  • Bansal, Y. ve Silakari, O., The therapeutic journey of benzimidazoles: A review, Bioorganic& Medicinal Chemistry, 20, 21, 6208-36, (2012) .
  • Salahuddin, Shaharyar, M. ve Mazumder, A., Benzimidazoles: A biologically active compounds, Arabian Journal of Chemistry, 10, 157–173, (2017).
  • Sharma, P., Rane, N. ve Gurram, V.K., Synthesis and QSAR studies of pyrimido [4, 5-d] pyrimidine- 2, 5-dione derivatives as potential antimicrobial agents. Bioorganic & Medicinal Chemistry Letters, 14, 4185–4190, (2004).
  • Sharma, S., Gangal, S. ve Rauf, A., Convenient one-pot synthesis of novel 2-substituted benzimidazoles, tetrahydrobenzimidazoles and imidazoles and evaluation of their in vitro antibacterial and antifungal activities, European Journal of Medicinal Chemistry, 44, 1751-1757, (2009).
  • Eren, B. ve Bekdemir, Y., Simple, mild and highly efficient synthesis of 2-substituted benzimidazoles and bisbenzimidazoles, Quimica Nova, 37, 4, 643-647, (2014).
  • Eren, B. ve Unal, A., Molecular structure and spectroscopic analysis of 1,4-Bis(1-methyl-2-benzimidazolyl)benzene; XRD, FT-IR, dispersive-Raman, NMR and DFT studies, Spectrochimica Acta Part A, 103, 222–231, (2013).
  • NCCLS Standarts. Clinical and Laboratory Standards Institute, Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th edition, CLSI document M7-A7, Clinical Laboratory Standards Institute, Wayne, PA, (2007).
  • Wiegand, I., Hilpert, K. ve Hancock, R. E. W., Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nature Protocols, 3, 163−175 (2008).
  • Sarker, S. D., Nahar, L. ve Kumarasamy, Y., Microtitre platebased antibacterial assay incorporating resazurin as an indicator of cell growth, and its application in the in vitro antibacterial screening of phytochemicals, Methods, 42, 321−324 (2007).
  • Isik, K. ve Özdemir-Kocak, F., Antimicrobial activity screening of some sulfonamide derivatives on some Nocardia species and isolates, Microbiological Research, 164, 49−58 (2009).
  • Gülay, Z., Antibiyotik duyarlılık testlerinin yorumu, Toraks Dergisi, 3,1, 75-88, (2002).
  • Abdel Ghani, N.T. ve Mansour, A. M., Novel Pd(II) and Pt(II) complexes of N,N-donor benzimidazole ligand: Synthesis, spectral, electrochemical, DFT studies and evaluation of biological activity, Inorganica Chimica Acta, 373, 249–258, (2011).
  • Unal, A. ve Eren, B., FT-IR, dispersive Raman, NMR, DFT and antimicrobial activity studies on 2-(Thiophen-2-yl)-1H-benzo[d]imidazole, Spectrochimica Acta Part A, 114, 129–136, (2013).
  • Kenchappa, R., Bodke, Y.D., Telkar, S. ve M. Aruna, S., Antifungal and anthelmintic activity of novel benzofuran derivatives containing thiazolo benzimidazole nucleus: an in vitro evaluation, Journal of Chemical Biology, 10, 11–23, (2017).
  • Sharma , M. C., Structural insight for (6-oxo-3-pyridazinyl)-benzimidazoles derivatives as angiotensin II receptor antagonists: QSAR, pharmacophore identification and kNNMFA approach, Journal of Saudi Chemical Society, 19,3, 265-273, (2012).
  • Sharma, D., Narasimhan, B., Kumar, P. ve Jalbout, A., Synthesis and QSAR evaluation of 2-(substituted phenyl)-1Hbenzimidazoles and [2-(substituted phenyl)-benzimidazol-1-yl]-pyridin-3-yl-methanones, European Journal of Medicinal Chemistry, 44, 1119-1127, (2009).
  • Abdel Ghani, N.T. ve Mansour, A. M., Novel Ni(II) and Zn(II) complexes coordinated by 2-arylaminomethyl-1Hbenzimidazole: Molecular structures, spectral, DFT studies and evaluation of biological activity, Inorganica Chimica Acta, 104, 134-142, (2013).
Toplam 22 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Mühendislik
Bölüm Araştırma Makalesi
Yazarlar

Fadime Özdemir Koçak 0000-0001-6608-0398

Bilge Eren 0000-0001-9775-9360

Yayımlanma Tarihi 15 Mart 2019
Gönderilme Tarihi 26 Kasım 2017
Yayımlandığı Sayı Yıl 2019 Cilt: 21 Sayı: 1

Kaynak Göster

APA Özdemir Koçak, F., & Eren, B. (2019). Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 21(1), 94-105. https://doi.org/10.25092/baunfbed.522970
AMA Özdemir Koçak F, Eren B. Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi. BAUN Fen. Bil. Enst. Dergisi. Mart 2019;21(1):94-105. doi:10.25092/baunfbed.522970
Chicago Özdemir Koçak, Fadime, ve Bilge Eren. “Benzimidazol halkasının Antimikrobiyal Aktivitesine Etki Eden yapısal faktörlerin Disk difüzyon Ve mikrodilüsyon Metodu Ile ayrıntılı Incelenmesi”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 21, sy. 1 (Mart 2019): 94-105. https://doi.org/10.25092/baunfbed.522970.
EndNote Özdemir Koçak F, Eren B (01 Mart 2019) Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 21 1 94–105.
IEEE F. Özdemir Koçak ve B. Eren, “Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi”, BAUN Fen. Bil. Enst. Dergisi, c. 21, sy. 1, ss. 94–105, 2019, doi: 10.25092/baunfbed.522970.
ISNAD Özdemir Koçak, Fadime - Eren, Bilge. “Benzimidazol halkasının Antimikrobiyal Aktivitesine Etki Eden yapısal faktörlerin Disk difüzyon Ve mikrodilüsyon Metodu Ile ayrıntılı Incelenmesi”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi 21/1 (Mart 2019), 94-105. https://doi.org/10.25092/baunfbed.522970.
JAMA Özdemir Koçak F, Eren B. Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi. BAUN Fen. Bil. Enst. Dergisi. 2019;21:94–105.
MLA Özdemir Koçak, Fadime ve Bilge Eren. “Benzimidazol halkasının Antimikrobiyal Aktivitesine Etki Eden yapısal faktörlerin Disk difüzyon Ve mikrodilüsyon Metodu Ile ayrıntılı Incelenmesi”. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, c. 21, sy. 1, 2019, ss. 94-105, doi:10.25092/baunfbed.522970.
Vancouver Özdemir Koçak F, Eren B. Benzimidazol halkasının antimikrobiyal aktivitesine etki eden yapısal faktörlerin disk difüzyon ve mikrodilüsyon metodu ile ayrıntılı incelenmesi. BAUN Fen. Bil. Enst. Dergisi. 2019;21(1):94-105.