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1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri

Year 2020, Volume: 10 Issue: 1, 1 - 5, 31.01.2020
https://doi.org/10.33631/duzcesbed.593379

Abstract

Amaç: Antifungal etkili ilaçların düzensiz
kullanımı ile artan direnç gelişimi ve immün yetmezliği olan hastaların
sayısındaki artış nedeniyle, son yıllarda fungal enfeksiyonların tedavisindeki
başarısızlık giderek artmaktadır. Bu sorun, daha etkin yeni antifungal ilaçlara
olan ihtiyacı doğurmaktadır. Günümüzde antiülseratif, antihelmintik, antiviral,
antihistaminik, antiinflamatuar ve antioksidan etkileri nedeniyle pek çok tedavi
alanında kullanılmakta olan benzotiyazol türevi bileşikler dikkat çekmektedir.
Benzotiyazol halkası, DNA bazlarının (pürin ve pirimidin çekirdekleri) temel
yapılarının izosteri olduğundan ve triptofan gibi aminoasitlerin doğal olarak
yapısında bulunduğundan canlı organizmalar tarafından tanınmaktadır. Pek çok
araştırma, benzotiyazol halkasının antifungal aktivitesini de kanıtlamıştır.

Gereç ve
Yöntemler:
Beş
yeni bileşikten oluşan 2-Sübstitüe-N-(6-(1,2,4-triazol-1-il)benzo[d]tiyazol-2-il)-asetamit
(5a-5e) serisi sentezlenmiştir. Elde edilen bileşiklerin yapıları FT-IR (fourier
dönüşümlü kızılötesi spektroskopisi), 1H-NMR (proton nükleer
manyetik rezonans), 13C-NMR (karbon nükleer manyetik rezonans) ve
kütle spektroskopisi verileri kullanılarak aydınlatılmıştır. Bileşiklerin in
vitro
antifungal aktivitesi microbroth dilüsyon yöntemi kullanılarak dört
farklı Candida türüne (Candida krusei, Candida albicans, Candida
parapsilosis
ve Candida globrata)
karşı değerlendirilmiştir. Ketakonazol referans ilaç olarak kullanılmıştır.

Bulgular:
Sentezlenen bileşiklerin minimum inhibitör konsantrasyon değerleri
incelendiğinde orta derecede antifungal aktivite gösterdikleri görülmektedir. Sentezlenen bileşikler içerisinde 5c kodlu bileşik C. glabrata ve C. albicans’a karşı referans
ilaçtan daha yüksek etki göstermiştir.

Sonuç: Sentezlenen bileşiklerin antifungal
potansiyelleri incelendiğinde umut verici sonuçlara ulaşıldığı görülmektedir.
Bu nedenle, bu çalışmanın sonuçlarına göre, projede kullanılan sentez
yöntemlerine bağlı olarak, sentezlenecek olan yeni bileşiklerin antifungal
aktivitelerinin araştırılması önerilmektedir.

References

  • 1. Shi C, Liu C, Liu J, Wang Y, Li J, Xiang M. Anti-Candida activity of new azole derivatives alone and in combination with fluconazole. Mycopathologia. 2015; 180(3-4): 203-7.
  • 2. Cao X, Sun Z, Cao Y, Wang R, Cai T, Chu W, et al. Design, synthesis, and structure–activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J Med Chem. 2014; 57(9): 3687-706.
  • 3. Ramirez-Villalva A, Gonzalez-Calderon D, Gonzalez-Romero C, Morales-Rodriguez M, Jauregui-Rodriguez B, Cuevas-Yanez E, et al. A facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity. Eur J Med Chem. 2015; 97: 275-9.
  • 4. Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends Microbiol. 2003; 11(6): 272-9.
  • 5. Heeres J, Meerpoel L, Lewi P. Conazoles. Molecules. 2010; 15(6): 4129-88.
  • 6. Danne AB, Choudhari AS, Chakraborty S, Sarkar D, Khedkar VM, Shingate BB. Triazole–diindolylmethane conjugates as new antitubercular agents: synthesis, bioevaluation, and molecular docking. Med Chem Comm. 2018; 9(7): 1114-30.
  • 7. Zhao D, Zhao S, Zhao L, Zhang X, Wei P, Liu C, et al. Discovery of biphenyl imidazole derivatives as potent antifungal agents: design, synthesis, and structure-activity relationship studies. Bioorg Med Chem. 2017; 25(2): 750-8.
  • 8. Maertens JA. History of the development of azole derivatives. Clin Microbiol Infect. 2004; 10(1): 1-10.
  • 9. Jacob KS, Ganguly S, Kumar P, Poddar R, Kumar A. Homology model, molecular dynamics simulation and novel pyrazole analogs design of Candida albicans CYP450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy. J Biomol Struct Dyn. 2016: 35(7): 1-44.
  • 10. Wani MY, Ahmad A, Shiekh RA, Al-Ghamdi KJ, Sobral AJ. Imidazole clubbed 1,3,4-oxadiazole derivatives as potential antifungal agents. Bioorg Med Chem. 2015; 23(15): 4172-80.
  • 11. Ayhan G. Yeni Bazı antifungal bileşiklerin sentezleri üzerinde çalışmalar [Yüksek Lisans Tezi]. Ankara: Ankara Üniversitesi; 1988.
  • 12. EUCAST. Definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. 2008; 14(4): 398-405.

Synthesis and Antifungal Activities of Benzothiazole Derivatives Bearing a 1,2,4-Triazole Moiety

Year 2020, Volume: 10 Issue: 1, 1 - 5, 31.01.2020
https://doi.org/10.33631/duzcesbed.593379

Abstract

Aim: In recent years, therapy of
fungal infections failure have increased because of the growing of multi-drug
resistance due to anomalous used of antifungal drugs and number of
immunocompromised patients who are susceptible to these infections. Hence there
was need to most effective novel antifungal compounds on microorganisms.
Nowadays, benzothiazole derivatives of used for various therapies due to
antiulcerative, antihelmintic, antiviral, antihistaminic, antiinflammatory and
antioxidant activities have been prominent. Benzothiazole ring was also
recognized by organism; because of they were isosteres of basic structures of
DNA bases (purine and pyrimidine moieties) and tryptophane amino acids.
Additionally, researches have showed that antifungal activities of
benzothiazole derivatives.

Material and Methods: A series of five new
compounds of 2-Substituted-N-(6- (1,2,4-triazol-1-yl)benzo[d]thiazol-2-yl)-acetamide
(
5a-5e) derivatives were
synthesized. The structures of the obtained compounds were elucidated using by
FT-IR (fourier transform infrared
spectroscopy
), 1H-NMR
(
proton nuclear magnetic resonance), 13C-NMR (carbon nuclear
magnetic resonance) and mass spectroscopy data. In vitro antifungal
activity of the compounds against four Candida strains (Candida crusei, Candida albicans, Candida
parapsilosis
and Candida globrata)
was evaluated by microbroth dilution method.
Ketaconazole was used as a
reference drug.

Results: When the mininum inhibitor concentration values of the synthesized compounds were examined, it
was seen that they showed moderate antifungal activity.
Among the synthesized
compounds, the compound
5c had a higher effect against C. glabrata and C.
albicans
than the reference drug.







Conclusion: When the antifungal
potentials of the synthesized compounds are examined, it is seen that promising
results are reached. Therefore, according to the results of this study, it is
suggested to investigate the antifungal activities of the new compounds to be synthesized,
depending on the synthesis methods used in the project.

References

  • 1. Shi C, Liu C, Liu J, Wang Y, Li J, Xiang M. Anti-Candida activity of new azole derivatives alone and in combination with fluconazole. Mycopathologia. 2015; 180(3-4): 203-7.
  • 2. Cao X, Sun Z, Cao Y, Wang R, Cai T, Chu W, et al. Design, synthesis, and structure–activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility. J Med Chem. 2014; 57(9): 3687-706.
  • 3. Ramirez-Villalva A, Gonzalez-Calderon D, Gonzalez-Romero C, Morales-Rodriguez M, Jauregui-Rodriguez B, Cuevas-Yanez E, et al. A facile synthesis of novel miconazole analogues and the evaluation of their antifungal activity. Eur J Med Chem. 2015; 97: 275-9.
  • 4. Odds FC, Brown AJ, Gow NA. Antifungal agents: mechanisms of action. Trends Microbiol. 2003; 11(6): 272-9.
  • 5. Heeres J, Meerpoel L, Lewi P. Conazoles. Molecules. 2010; 15(6): 4129-88.
  • 6. Danne AB, Choudhari AS, Chakraborty S, Sarkar D, Khedkar VM, Shingate BB. Triazole–diindolylmethane conjugates as new antitubercular agents: synthesis, bioevaluation, and molecular docking. Med Chem Comm. 2018; 9(7): 1114-30.
  • 7. Zhao D, Zhao S, Zhao L, Zhang X, Wei P, Liu C, et al. Discovery of biphenyl imidazole derivatives as potent antifungal agents: design, synthesis, and structure-activity relationship studies. Bioorg Med Chem. 2017; 25(2): 750-8.
  • 8. Maertens JA. History of the development of azole derivatives. Clin Microbiol Infect. 2004; 10(1): 1-10.
  • 9. Jacob KS, Ganguly S, Kumar P, Poddar R, Kumar A. Homology model, molecular dynamics simulation and novel pyrazole analogs design of Candida albicans CYP450 lanosterol 14 α-demethylase, a target enzyme for antifungal therapy. J Biomol Struct Dyn. 2016: 35(7): 1-44.
  • 10. Wani MY, Ahmad A, Shiekh RA, Al-Ghamdi KJ, Sobral AJ. Imidazole clubbed 1,3,4-oxadiazole derivatives as potential antifungal agents. Bioorg Med Chem. 2015; 23(15): 4172-80.
  • 11. Ayhan G. Yeni Bazı antifungal bileşiklerin sentezleri üzerinde çalışmalar [Yüksek Lisans Tezi]. Ankara: Ankara Üniversitesi; 1988.
  • 12. EUCAST. Definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts. 2008; 14(4): 398-405.
There are 12 citations in total.

Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Research Articles
Authors

Ulviye Acar Çevik 0000-0003-1879-1034

Derya Osmaniye This is me 0000-0002-0499-436X

Publication Date January 31, 2020
Submission Date July 17, 2019
Published in Issue Year 2020 Volume: 10 Issue: 1

Cite

APA Acar Çevik, U., & Osmaniye, D. (2020). 1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, 10(1), 1-5. https://doi.org/10.33631/duzcesbed.593379
AMA Acar Çevik U, Osmaniye D. 1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri. J DU Health Sci Inst. January 2020;10(1):1-5. doi:10.33631/duzcesbed.593379
Chicago Acar Çevik, Ulviye, and Derya Osmaniye. “1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi Ve Antifungal Aktiviteleri”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10, no. 1 (January 2020): 1-5. https://doi.org/10.33631/duzcesbed.593379.
EndNote Acar Çevik U, Osmaniye D (January 1, 2020) 1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10 1 1–5.
IEEE U. Acar Çevik and D. Osmaniye, “1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri”, J DU Health Sci Inst, vol. 10, no. 1, pp. 1–5, 2020, doi: 10.33631/duzcesbed.593379.
ISNAD Acar Çevik, Ulviye - Osmaniye, Derya. “1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi Ve Antifungal Aktiviteleri”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi 10/1 (January 2020), 1-5. https://doi.org/10.33631/duzcesbed.593379.
JAMA Acar Çevik U, Osmaniye D. 1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri. J DU Health Sci Inst. 2020;10:1–5.
MLA Acar Çevik, Ulviye and Derya Osmaniye. “1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi Ve Antifungal Aktiviteleri”. Düzce Üniversitesi Sağlık Bilimleri Enstitüsü Dergisi, vol. 10, no. 1, 2020, pp. 1-5, doi:10.33631/duzcesbed.593379.
Vancouver Acar Çevik U, Osmaniye D. 1,2,4-Triazol Yapısı Taşıyan Benzotiyazol Türevlerinin Sentezi ve Antifungal Aktiviteleri. J DU Health Sci Inst. 2020;10(1):1-5.