Some New Bis-(1,2,4-Triazole) Compounds: Synthesis, Characterization and Urease Enzyme Inhibition

Yıl 2024, Cilt: 14 Sayı: 3, 1360 – 1370, 15.09.2024

Nesrin Ünal Karaali , Havva Nur Cihangir

https://doi.org/10.31466/kfbd.1459377

Öz

In this study, thiosemicarbazide derivatives (2a-c) were obtained from the reaction of acetohydrazide derivative 1,2,4-triazole compound (1) with methyl isothiocyanate, phenyl isothiocyanate, and 4-methylphenyl isothiocyanate compounds, respectively. Then, by intramolecular cyclization of 2a-c compounds, bis-(1,2,4-triazole) compounds (3a-c) were synthesized. The synthesized compounds’ chemical structures were verified using FT-IR, 1H-NMR, and 13C-NMR spectroscopic methods. In addition, the urease enzyme inhibition of the synthesized compounds was evaluated using the Weatherburn method in vitro. All newly synthesized compounds showed urease enzyme inhibition in the range of 15.00 ± 0.10 to 16.00 ± 0.25 IC50 (µg/mL) compared to standard thiourea (IC50 = 15.75 ± 0.15 µg/mL).

Anahtar Kelimeler

Bis-(1,2,4-triazole), Isothiocyanate, Thiosemicarbazide, Urease

Etik Beyan

no

Destekleyen Kurum

no

Proje Numarası

yok

Teşekkür

no

Kaynakça

• Amir, M., and Shikha, K. (2004). Synthesisand Anti-inflammatory, Analgesic, Ulserogenic and Lipid Peroxidation Activities of Some New 2-[(2,6-Dichloroanilino)phenyl]acetic Acid Derivatives. European Journal of Medicinal Chemistry, 39, 535–545.
• Akyüz, G., Emirik, M.,, Sökmen, B. B., and Menteşe, E. (2022). Synthesis and Docking Studies of Novel Benzimidazole Derivatives Containing Thiophene and Triazole Rings as Potential Urease Inhibitors. Russian Journal of Bioorganic Chemistry, 48, 87–95.
• Akyuz, G., and Mentese, E. (2023). Synthesis of New Coumarin-C3 Benzimidazole Hybrids and Their Urease Inhibition Studies. Letters in Organic Chemistry, 20, 9, 864–870.
• Bentley, A., Butters, M.S., Green, P., Learmonth, W. J., MacRae, J. A., Morland, M. C. G., Connor, O., and Skuse, J. (2002). The Discovery and Process Development of a Commercial Routeto the Water-Soluble Prodrug, Fosfluconazole. Organic Process Research& Development, 6, 109–112.
• Bekhit, A. A., El-Sayed, O. A., Aboulmagd, E., and Park, J. Y. (2004). Tetrazolo[1,5- a] quinoline as a potential promising new scaff old forthe synthesis of novel antiinflammatory and antibacterial agents. European Journal of Medicinal Chemistry, 39, 249–255.
• El-Khawass, S. D. M., and Habib, N. S. (1989). Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4- b][1,3,4]thiazinederivatives of benzotriazole. Journal of Heterocyclic Chemistry, 26, 177–181.
• Farghaly, A. M., Bekhit, A. A., and Park, J. Y. (2000). Design and synthesis of some oxadiazolyl, thiadiazolyl, thiazolidinyl, and thiazolylderivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Archiv der Pharmazie, 333, 53–57.
• Gupta, A., Unadkat, J. D., and Mao, Q. (2007). Interactions of Azole Antifungal Agents with theHuman Breast Cancer Resistance Protein (BCRP). Journal of Pharmaceutical Science, 96, 3226–3235.
• Kahveci, B., Yılmaz, F., Menteşe, E., and Ülker, S. (2015). Microwave-assistedsynthesis of some new coumarin derivativesin cluding 1,2,4-triazol-3-one and investigation of their biological activities. Chemistry of Heterocyclic Compounds, 51, 5, 447–456.
• Karaali, N. and Mentese, E. (2016). Synthesis and Study of Antitumor Activity of Some New 2-(4-Methoxybenzyl)-1H-Benzimidazole Derivatives Bearing Triazole, Oxadiazole and Ethanol Moiety. Revue Roumaine De Chimie, 61, 3, 187–192.
• Karaali, N., Atik, R., Baltas, N., Sasmaz, S., and Kahveci, B. (2019). Synthesis, Inhibitory Properties on The Metabolic Enzymes and Antioxidant Activity of A New Series Benzimidazole Derivatives. Revue Roumaine De Chimie, 64, 8, 719–726.
• Menteşe, E., Akyüz, G., Emirik, M., and Baltaş, N. (2019). Synthesis, in vitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole, thiadiazole and thiosemicarbazide functionalities. Bioorganic Chemistry, 83, 289–296.
• Ram, V. J., Ram, V. J., and Vlietinck, A. J. (1988). Synthesis and Pesticidal activities of Sulphides and Sulphones Derived frombis [4-Aryl-1,2,4-triazoline-5-thione-3- yl]alkane and 5-Phenyl-1,3,4-oxadiazole-2-thione. Journal of Heterocyclic Chemistry, 25, 253–259.
• Schiller, S. D., and Fung, H. B. (2007). Posaconazole: An extended spectrum triazole antifungalagent. Clinical Therapeutics, 29, 1862–1886.

Bazı Yeni Bis-(1,2,4-Triazol) Bileşikleri: Sentez, Karakterizasyon ve Üreaz Enzim İnhibisyonu

Yıl 2024, Cilt: 14 Sayı: 3, 1360 – 1370, 15.09.2024

Nesrin Ünal Karaali , Havva Nur Cihangir

https://doi.org/10.31466/kfbd.1459377

Öz

Bu çalışmada, asetohidrazid türevi 1,2,4-triazol bileşiğinin (1) sırasıyla etilizotiyosiyanat, fenilizotiyosiyanat ve 4-etilfenilizotiyosiyanat bileşikleri ile reaksiyonundan tiyosemikarbazid türevleri (2a-c) elde edilmiştir. Daha sonra, 2a-c bileşiklerinin intramoleküler siklizasyonu ile bis-(1,2,4-triazol) bileşikleri (3a-c) sentezlenmiştir. Sentezlenen bileşiklerin kimyasal yapıları FT-IR, 1H-NMR ve 13C-NMR spektroskopik yöntemleri kullanılarak doğrulandı. Ayrıca, sentezlenen bileşiklerin üreaz enzimi inhibisyonu in vitro Weatherburn yöntemi kullanılarak değerlendirildi. Yeni sentezlenen tüm bileşikler, standart tiyoüre (IC50 (µg/mL): 15.75 ± 0.15) ile karşılaştırıldığında 15.00 ± 0.10 ila 16.00 ± 0.25 IC50 (µg/mL) aralığında üreaz enzim inhibisyonu göstermiştir.

Anahtar Kelimeler

İzotiyosiyanat, Tiyosemikarbazi, Üreaz., Bis-(1,2,4-triazol)

Etik Beyan

Gerekli değil

Destekleyen Kurum

yok

Proje Numarası

yok

Teşekkür

yok

Kaynakça

• Amir, M., and Shikha, K. (2004). Synthesisand Anti-inflammatory, Analgesic, Ulserogenic and Lipid Peroxidation Activities of Some New 2-[(2,6-Dichloroanilino)phenyl]acetic Acid Derivatives. European Journal of Medicinal Chemistry, 39, 535–545.
• Akyüz, G., Emirik, M.,, Sökmen, B. B., and Menteşe, E. (2022). Synthesis and Docking Studies of Novel Benzimidazole Derivatives Containing Thiophene and Triazole Rings as Potential Urease Inhibitors. Russian Journal of Bioorganic Chemistry, 48, 87–95.
• Akyuz, G., and Mentese, E. (2023). Synthesis of New Coumarin-C3 Benzimidazole Hybrids and Their Urease Inhibition Studies. Letters in Organic Chemistry, 20, 9, 864–870.
• Bentley, A., Butters, M.S., Green, P., Learmonth, W. J., MacRae, J. A., Morland, M. C. G., Connor, O., and Skuse, J. (2002). The Discovery and Process Development of a Commercial Routeto the Water-Soluble Prodrug, Fosfluconazole. Organic Process Research& Development, 6, 109–112.
• Bekhit, A. A., El-Sayed, O. A., Aboulmagd, E., and Park, J. Y. (2004). Tetrazolo[1,5- a] quinoline as a potential promising new scaff old forthe synthesis of novel antiinflammatory and antibacterial agents. European Journal of Medicinal Chemistry, 39, 249–255.
• El-Khawass, S. D. M., and Habib, N. S. (1989). Synthesis of 1,2,4-triazole, 1,2,4-triazolo[3,4- b][1,3,4]thiazinederivatives of benzotriazole. Journal of Heterocyclic Chemistry, 26, 177–181.
• Farghaly, A. M., Bekhit, A. A., and Park, J. Y. (2000). Design and synthesis of some oxadiazolyl, thiadiazolyl, thiazolidinyl, and thiazolylderivatives of 1H-pyrazole as anti-inflammatory antimicrobial agents. Archiv der Pharmazie, 333, 53–57.
• Gupta, A., Unadkat, J. D., and Mao, Q. (2007). Interactions of Azole Antifungal Agents with theHuman Breast Cancer Resistance Protein (BCRP). Journal of Pharmaceutical Science, 96, 3226–3235.
• Kahveci, B., Yılmaz, F., Menteşe, E., and Ülker, S. (2015). Microwave-assistedsynthesis of some new coumarin derivativesin cluding 1,2,4-triazol-3-one and investigation of their biological activities. Chemistry of Heterocyclic Compounds, 51, 5, 447–456.
• Karaali, N. and Mentese, E. (2016). Synthesis and Study of Antitumor Activity of Some New 2-(4-Methoxybenzyl)-1H-Benzimidazole Derivatives Bearing Triazole, Oxadiazole and Ethanol Moiety. Revue Roumaine De Chimie, 61, 3, 187–192.
• Karaali, N., Atik, R., Baltas, N., Sasmaz, S., and Kahveci, B. (2019). Synthesis, Inhibitory Properties on The Metabolic Enzymes and Antioxidant Activity of A New Series Benzimidazole Derivatives. Revue Roumaine De Chimie, 64, 8, 719–726.
• Menteşe, E., Akyüz, G., Emirik, M., and Baltaş, N. (2019). Synthesis, in vitro urease inhibition and molecular docking studies of some novel quinazolin-4(3H)-one derivatives containing triazole, thiadiazole and thiosemicarbazide functionalities. Bioorganic Chemistry, 83, 289–296.
• Ram, V. J., Ram, V. J., and Vlietinck, A. J. (1988). Synthesis and Pesticidal activities of Sulphides and Sulphones Derived frombis [4-Aryl-1,2,4-triazoline-5-thione-3- yl]alkane and 5-Phenyl-1,3,4-oxadiazole-2-thione. Journal of Heterocyclic Chemistry, 25, 253–259.
• Schiller, S. D., and Fung, H. B. (2007). Posaconazole: An extended spectrum triazole antifungalagent. Clinical Therapeutics, 29, 1862–1886.

Toplam 14 adet kaynakça vardır.

Ayrıntılar

Kaynak Göster

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