Antibacterial and antioxidant activities of novel 2-ethoxy- 4-[(4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl)azomethine]- phenyl 3-methoxybenzoate derivatives

Abstract

In the present study, 3-alkyl/aryl-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) reacted with 3-ethoxy-4- (3-methoxybenzoxy)-benzaldehyde (2) to obtain the corresponding nine new 2-ethoxy-4-[(3-alkyl/aryl-4,5-dihydro-1H- 1,2,4-triazol-5-one-4-yl)azomethine]-phenyl 3-methoxybenzoates (3). The compounds 3 were also treated with 4- piperidinecarboxamide in the presence of formaldehyde according to the Mannich reaction to synthesize 2-ethoxy-4-{[3- alkyl/aryl-1-(4-piperidinecarboxamide-1-yl-methyl)-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl]-azomethine}-phenyl 3- methoxy-benzoates (4). The structures of Schiff base and Mannich base derivatives were identified with spectral methods. Antimicrobial and antioxidant screening were carried out and discussed. Mannich base derivatives were found to be more active than Schiff bases in the biological screening. The effect values of Mannich Base derivatives dominate Neomycin and Streptomycin antibiotics.

Keywords

• Schiff base
• Mannich base
• 1
• 2
• 4-triazole-5-one
• antimicrobial activity
• antioxidant activity

References

1. [1] Cortes J. Lantibiotics and similar peptides produced by and active on gram-positives: Discovery, development, and perspectives. In: Marinelli F, Genilloud O. (Eds). Antimicrobials. Springer, Berlin, Heidelberg, 2014, pp.141-158. https://doi.org/10.1007/978-3-642-39968-8_7
2. [2] Sahu JK, Ganguly S, Kaushik A. Triazoles: A valuable insight into recent developments and biological activities. Chin J Nat Med. 2013; 11: 456-465. https://doi.org/10.1016/S1875-5364(13)60084-9
3. [3] Gökce H, Akyıldırım O, Bahçeli S, Yüksek H, Gürsoy-Kol O. The 1-acetyl-3-methyl-4-[3-methoxy-4-(4-methylbenzoxy)benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-one molecule investigated by a joint spectroscopic and quantum chemical calculations. J Mol Struc. 2014; 1056–1057(1): 273–284. https://doi.org/10.1016/j.molstruc.2013.10.044
4. [4] Aktaş-Yokuş O, Yüksek H, Manap S, Aytemiz F, Alkan M, Beytur M, Gürsoy-Kol O. In-vitro biological activity of some new 1,2,4-triazole derivatives with their potentiometric titrations. Bulg Chem Commun. 2017; 49: 98–106.
5. [5] Yüksek H, Koca E, Gürsoy-Kol Ö, Akyıldırım O, Çelebier M. Synthesis, in vitro antioxidant activity, and physicochemical properties of novel 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. J Mol Liq. 2015; 206: 359–366. https://doi.org/10.1016/j.molliq.2015.02.038
6. [6] Khalid W, Badshah A, Khan A, Nadeem H, Ahmed S. Synthesis, characterization, molecular docking evaluation, antiplatelet and anticoagulant actions of 1,2,4 triazole hydrazone and sulphonamide novel derivatives. Chem Cent J. 2018; 12: 11. https://doi.org/10.1186/s13065-018-0378-5
7. [7] Tatar E, Küçükgüzel SG, Karakuş S, De Clercq E, Andrei G, Snoeck R, Pannecouque C, Öktem Okullu S, Ünübol N, Kocagöz T, Kalaycı S, Şahin F, Küçükgüzel İ. Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents. Marmara Pharm J. 2015; 19(2): 88–102. https://doi.org/10.12991/mpj.2015199639
8. [8] Wu Z, Li X, Chi C-L, Xu L, Sun, Y-Y, Chen B.-Q. Synthesis and antitumor effects of a new class of 1,2,4-triazole derivatives. Med Chem Res. 2021; 30: 142–151. https://doi.org/10.1007/s00044-020-02652-y

9. [9] Roman G. Mannich bases in medicinal chemistry and drug design. Eur J Med Chem. 2015; 89: 743-816. https://doi.org/10.1016/j.ejmech.2014.10.076
10. [10] Ünver Y, Deniz S, Çelik F, Akar Z, Küçük M, Sancak K. Synthesis of new 1,2,4-triazole compounds containing Schiff and Mannich bases (morpholine) with antioxidant and antimicrobial activities. J Enzyme Inhib Med Chem. 2016; 31(S3): 89–95. https://doi.org/10.1080/14756366.2016.1206088
11. [11] Wang BL, Zhang LY, Liu XH, Ma Y, Zhang Y, Li ZM, Zhang X. Synthesis, biological activities and SAR studies of new 3-substitutedphenyl-4-substituted-benzylideneamino-1,2,4-triazole Mannich bases and bis-Mannich bases as ketol-acid reductoisomerase inhibitors. Bioorg Med Chem Lett. 2017; 27(24): 5457-5462. https://doi.org/10.1016/j.bmcl.2017.10.065
12. [12] Manap S, Gürsoy-Kol Ö, Alkan M, Yüksek H. 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 J Chem Sect B. 2020; 59B(02): 271-282.
13. [13] Boy S, Aras A, Türkan F, Akyıldırım O, Beytur M, Karaman HS, Manap S, Yüksek H. Synthesis, spectroscopic analysis, and in vitro/in silico biological studies of novel piperidine derivatives heterocyclic Schiff-Mannich base compounds. Chem Biodivers. 2021; 18: e21004 https://doi.org/10.1002/cbdv.202100433
14. [14] Albelwi FF, Teleb M, Abu-Serie MM, Moaty MNAA, Alsubaie MS, Zakaria MA, El Kilany Y, Aouad MR, Hagar M, Rezki N. Halting tumor progression via novel non-hydroxamate triazole-based Mannich bases MMP-2/9 inhibitors; design, microwave-assisted synthesis, and biological evaluation. Int J Mol Sci. 2021; 22(19): 10324. https://doi.org/10.3390/ijms221910324
15. [15] Demirbas N, Karaoglu AŞ, Demirbas A, Sancak K. Synthesis and antimicrobial activities of some new 1-(5- phenylamino-[1,3,4]thiadiazol-2-yl]methyl-5-oxo-[1,2,4]triazole and 1-[4-phenyl-5-thioxo-[1,2,4]triazol-3-yl)methyl-5-oxo-[1,2,4]triazole derivatives. Eur J Med Chem. 2004; 39: 793-804. https://doi.org/10.1016/j.ejmech.2004.06.007
16. [16] Gupta D, Jain DK. Synthesis, antifungal and antibacterial activity of novel 1,2,4-triazole derivatives. J Adv Pharm Technol Res. 2015; 6: 141-146.
17. [17] Mohamed NG, Sheha MM, Hassan HY, Abdel-Hafez LJM, Omar FA. Synthesis, antimicrobial activity and molecular modeling study of 3-(5-amino-(2H)-1,2,4-triazol-3-yl]-naphthyridinones as potential DNA-gyrase inhibitors. Bioorg Chem. 2018; 81: 599-611. https://doi.org/10.1016/j.bioorg.2018.08.031
18. [18] Mammadbayli EH, Hajiyeva GE, Ibrahimli SI, Cafarova NA. Synthesis and antimicrobial activity of norbornene-containing Mannich Bases. Russ J Appl Chem. 2019; 92(8): 1161–1169. https://doi.org/10.1134/S1070427219080160
19. [19] Vhanale BT, Deshmukh NJ, Shinde AT. Synthesis, characterization, spectroscopic studies and biological evaluation of Schiff bases derived from 1–hydroxy-2-acetonapthanone. Heliyon. 2019; 5(11): e02774. https://doi.org/10.1016/j.heliyon.2019.e02774
20. [20] Gordon MH. The mechanism of antioxidant action in vitro. In: Hudson BJF. (Ed). Food Antioxidants. Elsevier Applied Food Science Series, Springer, Dordrecht, 1990, pp.1-18. https://doi.org/10.1007/978-94-009-0753-9_1
21. [21] İkizler A, Ün R. Reactions of ester ethoxycarbonylhydrazones with some amine type compounds. Chim Acta Turcia. 1979; 7: 269-290.
22. [22] İkizler A, Yüksek H. Acetylation of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Org Prep Proced Int. 1993; 25: 99-105. https://doi.org/10.1080/00304949309457935
23. [23] Perez C, Pauli M, Bazerque P. An antibiotic assay by agar-well diffusion method. Acta Biol Med Exp. 1990; 15: 113-115.
24. [24] Ahmad I, Mehmood Z, Mohammad F. Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol. 1998; 62(2): 183-193. https://doi.org/10.1016/S0378-8741(98)00055-5
25. [25] Oyaizu M. Studies on products of browning reaction. Antioxidative activities of products of browning reaction prepared from glucosamine. Japanese J Nutr Diet. 1986; 44(6): 307-315. https://doi.org/10.5264/eiyogakuzashi.44.307
26. [26] Blois M. Antioxidant determinations by the use of a stable free radical. Nature. 1958; 181: 1199-1200. https://doi.org/10.1038/1811199a0
27. [27] Dinis TCP, Madeira VMC, Almeida LM. Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys. 1994; 315(1): 161-169. https://doi.org/10.1006/abbi.1994.1485