Synthesis and Biological Evaluation of 3-Alkyl(Aryl)-4-(4-methylthio-benzylideneamino)-4,5-dihidro-1H-1,2,4-triazol-5-one Derivatives

Abstract

In the present study, 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (3c, f, e) reacted with 4-methylthiobenzaldehyde to afford 3-alkyl(aryl)-4-(4-methylthio-benzylideneamino)-4,5-dihidro-1H-1,2,4-triazol-5-ones (4c, f, e). The structures of three new compounds were established from the elemental analysis, IR, 1H NMR, and 13C NMR spectral data. The newly synthesized and recently synthesized 3-alkyl(aryl)-4-(4-methylthiobenzylideneamino)-4,5-dihidro-1H-1,2,4-triazol-5-one derivatives were analyzed using three methods for antioxidant activities. Compound 4a showed the best activity for the metal chelating effect. Furthermore, the compounds' antimicrobial activity was screened.

Keywords

• 1,2,4-triazole
• Synthesis
• Antioxidant activity
• Antimicrobial activity

References

1. Abbas, A., Nadeem, H., Khan, A. U., Ali, F., Afzaal, H., Nadhman, A., & Khan, I. (2017). Synthesis, characterization, antioxidant, antimicrobial, cytotoxic, anticancer, leishmanicidal, anti-inflammatory activities and docking studies of heterocyclic 1,3,4-oxadiazoles and 4-amino-1,2,4-triazoles derivatives. Journal of the Chemical Society of Pakistan, 39(4), 661–673.
2. Aboeldahab, A. M. A., Beshr, E. A. M., Shoman, M. E., Rabea, S. M., & Aly, O. M. (2018). Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation. European Journal of Medicinal Chemistry, 146, 79–92.
3. Abuelhassan, A. H., Badran, M. M., Hassan, H. A., Abdelhamed, D., Elnabtity, S., & Aly, O. M. (2018). Design, synthesis, anticonvulsant activity, and pharmacophore study of new 1,5-diaryl-1H-1,2,4-triazole-3-carboxamide derivatives. Medicinal Chemistry Research, 27(3), 928–938.
4. Ahmad, I., Mehmood, Z., & Mohammad, F. (1998). Screening of some Indian medicinal plants for their antimicrobial properties. Journal of Ethnopharmacology, 62(2), 183–193.
5. Aktas-Yokus, O., Yuksek, H., Manap, S., Aytemiz, F., Alkan, M., Beytur, M., & Gursoy-Kol, O. (2017). In-vitro biological activity of some new 1,2,4-triazole derivatives with their potentiometric titrations. Bulgarian Chemical Communications, 49(I), 98–106.
6. Bajpai, V. K., Rather, I. A., & Shukla, S. (2016). Microbes in Food and Health-Oxidative Stress: Role of NaturalAntioxidant Compounds (N. Garg, S. M. Abdel-Aziz, & A. Aeron (eds.)). Springer International Publishing: Switzerland.
7. Blois, M. (1958). Antioxidant Determinations by the Use of a Stable Free Radical. Nature, 181(4617), 1199–1200.
8. Dinis, T. C. P., Madeira, V. M. C., & Almeida, L. M. (1994). Action of Phenolic Derivatives (Acetaminophen, Salicylate, and 5-Aminosalicylate) as Inhibitors of Membrane Lipid Peroxidation and as Peroxyl Radical Scavengers. Archives of Biochemistry and Biophysics, 315(1), 161–169. Gupta, V. K., & Sharma, S. K. (2006). Plants as natural antioxidants. Natural Product Radiance, 5(4), 326–334.

9. Ikizler, A., & Un, R. (1979). Reactions of ester ethoxycarbonylhydrazones with some amine type compounds. Chimica Acta Turcia, 7, 269–290. Ikizler, A., & Yüksek, H. (1993). Acetylation of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Organic Preparations and Procedures International, 25(1), 99–105.
10. Iqbal, A. K. M., Khan, A. Y., Kalashetti, M. B., Belavagi, N. S., Gong, Y. D., & Khazi, I. A. M. (2012). Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring. European Journal of Medicinal Chemistry, 53, 308–315.
11. Li, Z., Cao, Y., Zhan, P., Pannecouque, C., Balzarini, J., & Clercq, E. De. (2013). Synthesis and anti-HIV evaluation of novel 1,2,4-triazole derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors. LETTERS IN DRUG DESIGN & DISCOVERY, 10(1), 27–34.
12. Manap, S., Gürsoy-Kol, Alkan, M., & Yüksek, H. (2020). Synthesis, in vitro antioxidant and antimicrobial activities of some novel 3-substitued-4-(3-methoxy-4-isobutyryloxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 59(2), 271–282.
13. Medetalibeyoğlu, H., Türkan, F., Manap, S., Bursal, E., Beytur, M., Aras, A., Akyıldırım, O., Kotan, G., Gürsoy-Kol, Ö., & Yüksek, H. (2023). Synthesis and acetylcholinesterase enzyme inhibitory effects of some novel 4,5-Dihydro-1H-1,2,4-triazol-5-one derivatives; an in vitro and in silico study. Journal of Biomolecular Structure and Dynamics, 41(10), 4286–4294.
14. Monaghan, R. L., & Barrett, J. F. (2006). Antibacterial drug discovery—Then, now and the genomics future. Biochemical Pharmacology, 71(7), 901–909.
15. Oyaizu, M. (1986). Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine. The Japanese Journal of Nutrition and Dietetics, 44(6), 307–315.
16. Perez, C., Pauli, M., & Bazerque, P. (1990). An antibiotic assay by agar-well diffusion method. Acta Biologiae et Medecine Experimentaalis, 15, 113–115.
17. Rathore, G., Suthar, M., Pareek, A., & Gupta, R. (2011). Nutritional antioxidants: A battle for better health. Journal of Natural Pharmaceuticals, 2(1), 2–14.
18. Yüksek, H., Akyıldırım, O., Yola, M. L., Gürsoy-Kol, Ö., Çelebier, M., & Kart, D. (2013). Synthesis, In Vitro Antimicrobial and Antioxidant Activities of Some New 4,5-Dihydro-1 H -1,2,4-triazol-5-one Derivatives. Archiv Der Pharmazie, 346(6), 470–480.
19. Yüksek, H., & Kardaş, F. (2022). Synthesis and Characterization of Novel Potential Biologically Active 3-Alkyl(Aryl)-4-(4-methylthiobenzylideneamino)-4,5-dihidro-1H-1,2,4-triazol-5-ones. Chemistry Research Journal, 7(3), 19–22.