DESIGN, SYNTHESIS, ANTIMICROBIAL AND ANTIFUNGAL ACTIVITIES OF NEW 1,2,4-TRIAZOLE DERIVATIVES CONTAINING 1H-TETRAZOLE MOIETY

Year 2020, Volume: 44 Issue: 1, 70 - 88, 31.01.2020

Yuliia Frolova , Andriy Kaplaushenko Nataliya Nagornaya

https://doi.org/10.33483/jfpau.574001

Cited By: 15

Abstract

Objective: Antimicrobials and
antifungals are the most acquired drugs in the world. Today, it becomes
necessary to create new drugs with antimicrobial and antifungal effect. The purpose of our research is the synthesis of new series
of 5-(1Н-tetrazole-1-yl)-4H-1,2,4-triazole-3-amine, the establishment of
physical-chemical, antimicrobial and antifungal properties for all synthesized
compounds.

Materials and
Methods: 5-(1Н-tetrazole-1-yl-methyl)-4H-1,2,4-triazole-3-yl-1-(alkyl-,
aryl-)-methanimines were synthesized by reacting of 5-(1H-tetrazole-1-yl-methyl)-4H-1,2,4-triazole-3-amine
with aldehydes in acetic acid. Then, sodium borohydride was selected as a
reducing agent, which allowed for the restoration of the double bond. The
structures of synthesized compounds were confirmed by IR, ¹H NMR and
mass spectra. The synthesized compounds were evaluated for antimicrobial and antifungal activity
by "serial dilutions" method.

Result and Discussion: During the synthetic studies the new
series of 22 compounds were obtained. The
5-(1Н-tetrazole-1-yl-methyl)-4H-1,2,4-triazole-3-yl-1-(5-nitrofuran-2-yl)methanimine
was observed to be most possessing good antimicrobial and antifungal and has
exceeded the reference standard for Staphylococcus aureus (12,5/25 mg/ml),
Escherichia coli (50/100 mg/ml), Pseudomonas Aeruginosa (100/200 mg/ml), Candida
albicans (50/50 mg/ml).

Keywords

1Н-tetrazole, 1.2.4-triazole, antimicrobial and antifungal activity

Supporting Institution

We acknowledge complete support of the Zaporozhye State Medical University.

Thanks

We thank rector of Zaporozhye State Medical University Prof. Yu. M. Kolesnyk for his help and support.

1H-TETRAZOL İÇEREN YENİ 1,2,4-TRİAZOL TÜREVLERİNİN TASARIMI, SENTEZİ, ANTİMİKROBİYAL VE ANTİFUNGAL AKTİVİTELERİ

Abstract

        Amaç: Antimikrobiyal ve antifungal ilaçlar dünyada en yaygın
ilaç türlerindendir. Günümüzde mikroplara ve mantarlara karşı yeni ilacın
üretilmesine ihtiyaç duyulur. Araştırmamızın amacı, 5-(1Н-tetrazol-1-il)-4Н-1,2,4-triazol-3-amin
türevi yeni bileşiklerin sentezi ile sentez edilmiş bileşiklerin fizikokimyasal,
antimikrobiyal ve antifungal özelliklerinin tespit edilmesidir.

       
Gereç ve Yöntem: 5-(1Н-tetrazol-1-ilmetil)-4Н-1,2,4-triazol-3-il-1-(alkil-,
aril-)-metanim, 5-(1H-tetrazol-1-ilmetil)-4H-1,2,4-triazol-3-amin’in sirke
asidinde aldehitler ile etkileşimi sonucunda sentez edilmiştir. Bir sonraki
aşamada indirgen olarak sodyum borohidrür kullanıldığı için ikili bağ yeniden
kurulabilmiştir. Sentez edilmiş bileşiklerin yapıları, kızılaltı, nükleer
manyetik rezonans ve kütle spektroskopisi ile doğrulanır. Sentez edilmiş bileşikler
mikrop ve mantarlara karşı aktivite konusunda serili dilüsyon metodu ile
denetlenmiştir.

        Sonuç ve Tartışma: Sentetik
araştırmaların sonucunda 22 bileşikten oluşan yeni seri elde edilmiştir. 5-(1Н-tetrazol-1-ilmetil)-4Н-1,2,4-triazol-3-il-1-(5-nitrofuran-2-il)metanimin
en iyi antimikrobiyal ve antifungal etkisine sahip olup Staphylococcus aureus
(12,5/25 mg/ml), Escherichia coli (50/100 mg/ml), Pseudomonas aeruginosa
(100/200 mg/ml), Candida albicans (50/50 mg/ml) için karşılaştırmalı ilacı
geçtiğini tespit edilmiştir.

Keywords

1.2.4-triazol, 1Н-tetrazol, antimikrobiyal ve antifungal aktivite

References

• 1. Sehrawat, R., Maithani, M., Singh,R. (2010). Regulatory Aspects in Development of Stability-Indicating Methods: A Review. Chromatographia, 72 (1/2), 1–6.
• 2. Blessy, M, Ruchi, D.P., Prajesh, N.Pr., Agrawal, Y.K. (2014). Development of forced degradation and stability indicating studies of drugs-A review. Journal of Pharmaceutical Analysis; 4(3), 159–165.
• 3. Klick, S., Muijselaar, P.G., Waterval, J., Eichinger, Th., Korn, C., Gerding, Th.K., Debets, Al.J., Van de Griend, C.S., Van den Beld, C., Somsen, G.W. and De Jong, G.J. (2005). Stress Testing of Drug Substances and Drug Products. Pharmaceutical Technology, FEBRUARY; 48–66.
• 4. Chakravarthy, V.A., Sailaja, B.B.V., Kumar, A.P. (2015). Stability-Indicating RP-HPLC Method for Simultaneous Estimation of Enrofloxacin and Its Degradation Products in Tablet Dosage Forms. Journal of Analytical Methods in Chemistry, 2015, 1 – 11.
• 5. Ahirrao, V.K., Patil, C.S., Bembalkar, S.R., Katariya, M.V., Sonnekar, V.S., Marathe, R.P., Nawale,R. B.,Pawar, R. P.(2012). Stress degradation studies of dronedarone in pharmaceutical dosage form by a validated stability-indicating LC method. Journal of the Chilean Chemical Society, 57(3); 1272 – 1276.
• 6. Patel, J. K., Patel, N. K. (2014). Stability-Indicating RP-HPLC Method for the Determination of Ambrisentan and Tadalafil in Pharmaceutical Dosage Form. Scientia Pharmaceutica, 82, 749–763.
• 7. Parchenko, V. V., Panasenko, O. I., Knysh, E. G., Vasyuk S. O., Tarkhanova, O. O. (2009). Working out of methods quantitative determination piperidiniy 2-[5-(furan-2-il)-4-phenil-1,2,4-triazol-3-ilthio]acetate in the substance. Ukrainskyi biofarmatsevtychnyi zhurnal, 4, 44–45.
• 8. Parchenko, V.V., Panasenko, O.I., Knysh, E.G., Vasiuk, S.O., Tarkhanova, O. O. (2009). Qualitative and quantitative determination of the Piperidinium 2-((5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)acetate 1% and 2,5% solutions. Zaporozhye medical journal, 3, 111–112.
• 9. Varynskyi, B. O., Parchenko, V.V., Kaplaushenko, А. G. (2017). Development and validation of HPLC-DAD method of determination piperidinium 2-((5-(furan-2-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)acetate in 1 % solution, Zaporozhye medical journal, 19 (6), 827-832.
• 10. Parchenko, V. (2006). Synthesis, physicochemical and biological properties of derivatives of 1,2,4-triazoles-3-thione containing core furan. Candidate of Pharm Scithesis, Zaporozhye State Medical University, Zaporozhye, 208 p.
• 11. Parchenko, V. (2014). Synthesis, transformation, physico-chemical and biological properties in a number of 5-furyl-substituted 1,2,4-triazole-3-thiones. Dr. Pharmacist Sciences thesis, Zaporozhye State Medical University, Zaporozhye, 460 p.
• 12. Tietze, L.F., Eicher, Th. (1991). Reaktionen und Synthesen im organisch‐chemischen Praktikum und Forschungs laboratorium. 2. Aufl., Georg Thieme Verlag, Stuttgart – NewYork. DM 68, 672 S.