SYNTHESIS, ANTIMICROBIAL AND ANTIFUNGAL ACTIVITY OF YLIDENHYDRAZIDES OF 2-((4-R-5-R1-4H-1,2,4-TRIAZOL-3-YL)THIO)ACETALDEHYDES

Abstract

Objective: The aim of this work is the synthesis and studying of antimicrobial and antifungal properties of the ylidenhydrazides of 2-((4-R-5-R1-4H-1,2,4-triazol-3-yl)thio)acetaldehydes with the establishment of structure-activity relationships of the synthesized compounds.

Material and Method: Determination of antimicrobial and antifungal activity was performed by disc-diffusion method (DDM) on series of gram positive and gram negative bacteria such as Corynebacterium pseudodiphtheriticum, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus vulgaris, Escherichia coli, Salmonella spp., Staphylococcus saprophyticus, Staphylococcus aureus, Streptococcus pyogenes, Candida.

Result and Discussion: A new series of ylidenhydrazides of 2-((4-R-5-R1-4H-1,2,4-triazol-3-yl)thio)acetaldehydes were synthesized and their structures were confirmed by modern methods of instrumental analysis: IR and 1H-spectroscopy, elemental analysis and GS\MS method. For 13 compounds, the antimicrobial and antifungal activities were studied on 10 strains of microorganisms in 3 different concentrations (0.1; 0.2; 0.5%). According to the results of the study, some regularities of the structure-activity relationship have been established. The obtained results can serve as a basis for the targeted search compounds with pronounced antibacterial action. An increasing the concentration of tested compounds predictably lead to increase on antimicrobial activity in almost all cases. The most active compound in our study is N'-(2-((5-methyl-4H-1,2,4-triazol-3-yl)thio)ethylidene)-4-nitrobenzohydrazide 3i (ZOI for Sta.s. and Sp in 0.5% concentration is 25 and 26 mm, respectively).

Keywords

• 1.2.4-triazole
• synthesis
• antimicrobial activity

2-((4-R-5-R1-4H-1,2,4-TRİAZOL-3-İL)TİYO)ASETALDEHİTLERİN İLİDENHİDRAZİDLERİNİN SENTEZİ, ANTİMİKROBİYAL VE ANTİFUNGAL AKTİVİTESİ

Abstract

Amaç: Bu çalışmanın amacı, 2-(4-R-5-R1-4H-1,2,4-triazol-3-yl)tio)asetaldehitlerin bir dizi ilidenhidrazidinin sentezi ve antimikrobiyal ve antifungal özelliklerinin yapı-etki ilişkisi kurularak incelenmesidir.
Gereç ve Yöntem: Antimikrobiyal ve antifungal aktivitenin tespiti, aşağıdaki mikroorganizma türleri için disk-difüzyon yöntemi ile gerçekleştirilmiştir: Corynebacterium pseudodiphtheriticum, Pseudomonas aeruginosa, Enterococcus faecalis, Proteus vulgaris, Escherichia coli, Salmonella spp., Staphylococcus saprophyticus, Staphylococcus aureus, Streptococcus pyogenes, Candida.
Sonuç ve Tartışma: Yeni 2-((4-R-5-R1-4H-1,2,4-triazol-3-yl)tio)asetaldehitlerin ilidenhidrazidleri sentezlenmiştir. Yapıları modern analiz yöntemleri olan IR, 1H spektroskopisi, element analizi ve GS\MS yöntemi ile doğrulanmıştır. Sentezlenen 13 bileşik için antimikrobiyal aktivite, 3 farklı konsantrasyonda (0.1; 0.2; % 0.5) 10 mikroorganizma suşu üzerinde çalışılmıştır. Çalışmanın sonuçlarına göre, bazı yapı-etki ilişkileri kurulmuştur. Elde edilen sonuçlar, belirgin antibakteriyel etkiye sahip bileşikler için hedeflenen araştırmanın temelini oluşturabilir. Test maddelerinin konsantrasyonunun artırılmasının, neredeyse tüm durumlarda antimikrobiyal etkiyi artıracağı tahmin edilmektedir. Çalışmamızdaki en aktif bileşik N'-(2-((5-metil-4H-1,2,4-triazol-3-il)tiyo)etiliden)-4-nitrobenzohidrazid 3i’dir (ZOI Sta.s. ve Sp. - 25 ve 26 mm % 0,5 konsantrasyonda).

Keywords

• Antimikrobiyal aktivite
• sentez
• 1,2,4-triazol

References

1. Mathers, C. D. (2020). History of global burden of disease assessment at the World Health Organization. Archives Of Public Health, 78(1), 1-13. [CrossRef]
2. World Health Statistic Web site (2020). Retrieved Mach 01, 2020, from https://apps.who.int/iris/bitstream/handle/10665/332070/9789240005105-eng.pdf. Accessed date 01.05.2021.
3. Wilson, D. N., Hauryliuk, V., Atkinson, G. C., O’Neill, A. J. (2020). Target protection as a key antibiotic resistance mechanism. Nature Reviews Microbiology, 18(11), 637-648. [CrossRef]
4. Samelyuk, Y. G., Kaplaushenko, A. G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, containing methoxyphenyl substituents at C5 atoms, their antipyretic activity, propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121. Retrieved May 01, 2021, from https://www.jocpr.com/articles/synthesis-of-3alkylthiosulfo124triazoles-containing-methoxyphenyl-substituents-at-c5-atoms-their-antipyretic-activity-pr.pdf
5. Bushueva, I., Parchenko, V., Shcherbyna, R., Safonov, A., Kaplaushenko, A., Gutyj, B., Hariv, I. (2017). Tryfuzol-new original veterinary drug. J. Fac. Pharm. Ankara/Ankara Ecz. Fak. Derg, 41(1), 42-49. [CrossRef]
6. Shcherbyna, R., Parchenko, V., Martynyshyn, V., Hunchak, V. (2018). Evaluation of acute and subacute toxicity of oil liniment based on 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazol-3-yl)methyl)morpholine. J. Fac. Pharm. Ankara/Ankara Ecz. Fak. Derg, 42 (1), 43-52. Retrieved May 01, 2021, from https://dergipark.org.tr/en/pub/jfpanu/issue/42653/514314
7. Safonov, A. A. (2018). Derivatives of 3-(alkylthio)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-4-amines as anti-fatigue substances. Indonesian Journal of Pharmacy/Majalah Farmasi Indonesia, 29(3). [CrossRef]
8. Aljamali, N. M., Mahmood, R. M. U., Baqi, R. A. (2020). Review on preparation and application fields of triazole & tetrazole derivatives. International Journal of Analytical and Applied Chemistry, 6(1), 50-60p. Retrieved May 01, 2021, from http://chemical.journalspub.info/

9. Sumrra, S. H., Habiba, U., Zafar, W., Imran, M., Chohan, Z. H. (2020). A review on the efficacy and medicinal applications of metal-based triazole derivatives. Journal of Coordination Chemistry, 73(20-22), 2838-2877. [CrossRef]
10. Frolova, Y., Kaplaushenko, A., Nagornaya, N. (2020). Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-triazole derivatives containing 1H-tetrazole moiety. Ankara Üniversitesi Eczacılık Fakültesi Dergisi, 44(1), 70-88. [CrossRef]
11. Shcherbyna, R, Vashchyk, Y. (2019). The research of 1,2,4-triazole derivatives hepatoprotective activity under tetracycline and infectious hepatitis. Journal of Faculty of Pharmacy of Ankara University, 43 (2), 135-146 . [CrossRef]
12. Peyton, L. R., Gallagher, S., Hashemzadeh, M. (2015). Triazole antifungals: a review. Drugs Today (Barc), 51(12), 705-718. [CrossRef]
13. Christenson, J. C., Korgenski, E. K., Relich, R. F. (2018). Laboratory diagnosis of infection due to bacteria, fungi, parasites, and rickettsiae. In: Sarah S. Long (Ed.), In Principles and Practice of Pediatric Infectious Diseases, (pp. 1422-1434). Philadelphia: Elsevier.
14. Tenover, F. (2015). Antimicrobial susceptibility testing. In: Thomas M. Schmidt (Ed.), Reference Module In Biomedical Sciences, (pp. 166-175). Amsterdam: Elsevier.
15. Principles of anti-infective therapy Web site (2015). Retrieved January 01, 2015, from https://yixueshu.gitee.io/cecil/ Accessed date 01.05.2021.