Skip to main content
SpringerLink
Log in

Synthesis and biological evaluation of new 1,2,4-triazole derivatives with their potentiometric titrations

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

In the present study, 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1a, b, d–g) reacted with 3-phenoxybenzaldehyde to afford 3-alkyl(aryl)-4-(3-phenoxy-benzylidenamino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2a, b, d–g). Then, the acetylation reactions of compounds 2a and 2d–g were investigated. The structures of 11 new compounds were established from the elemental analysis, IR, 1H NMR, 13C NMR, MS, and UV spectral data. The synthesized compounds were analyzed for their in vitro potential antioxidant activities in three different methods. Compounds 2f and 3d showed best activity for the iron binding. Moreover, the compounds 2 were titrated potentiometrically with tetrabutylammonium hydroxide in four non-aqueous solvents (isopropyl alcohol, tert-butyl alcohol, acetonitrile, and N,N-dimethyl formamide). Thus, the half-neutralization potential values and the corresponding pK a values were determined in all cases. Furthermore, these 11 new compounds and 13 recently reported 3-alkyl(aryl)-4-(2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a–g) and 1-acetyl-3-alkyl(aryl)-4-(2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-ones (5a, b, d–g) were screened for their antimicrobial activities.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Ahmad I, Mehmood Z, Mohammad F (1998) Screening of some Indian medicinal plants for their antimicrobial properties. J Ethnopharmacol 62:183–193

    Article  CAS  PubMed  Google Scholar 

  • Bahceci S, Yuksek H, Ocak Z, Azakli I, Alkan M, Özdemir M (2002) Synthesis and potentiometric titrations of some new 4-(benzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives in non-aqueous media. Collect Czech Chem Commun 67:1215–1222

    Article  CAS  Google Scholar 

  • Baumann J, Wurn G, Bruchlausen FV (1979) Prostaglandin synthetase inhibiting O2: radical scavenging properties of some flavonoids and related phenolic compounds. N-S Arch Pharmacol 308:R27

    Google Scholar 

  • Bayrak H, Demirbas A, Karaoglu SA, Demirbas N (2009) Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities. Eur J Med Chem 44:1057–1066

    Article  CAS  PubMed  Google Scholar 

  • Blois MS (1958) Antioxidant determinations by the use of a stable free radical. Nature 181:1199–1200

    Article  CAS  Google Scholar 

  • Bonde CG, Gaikwad NJ (2004) Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents. Bioorg Med Chem 12:2151–2161

    Article  CAS  PubMed  Google Scholar 

  • Calis I, Hosny M, Khalifa T, Nishibe S (1993) Secoiridoids from Fraxinus angustifolia. Phytochemistry 33:1453–1456

    Article  CAS  Google Scholar 

  • Demirbas A, Kula I, Erdogan Y, Aslan A, Yayli N, Karslioglu S (1998) Non-aqeous medium titration of some acidic compounds. Energy Educ Sci Tech 1:13–16

    CAS  Google Scholar 

  • Dinis TCP, Madeira VMC, Almeida LM (1994) Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid-peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 315:161–169

    Article  CAS  PubMed  Google Scholar 

  • Duh PD, Tu YY, Yen GC (1999) Antioxidant activity of water extract of Harng Jyur (Chrysanthemum morifolium Ramat). Food Sci Technol Leb 32:269–277

    Article  CAS  Google Scholar 

  • Finefrock AE, Bush AI, Doraiswamy PM (2003) Current status of metals as therapeutic targets in Alzheimer’s disease. J Am Geriatr Soc 51:1143–1148

    Article  PubMed  Google Scholar 

  • Frey PA, Kokesh FC, Westheimer FH (1971) A reporter group at active site of acetoacetate decarboxylase. I. Ionization constant of the nitrophenol. J Am Chem Soc 93:7266–7269

    Article  CAS  PubMed  Google Scholar 

  • Gordon MH (1990) Food antioxidants. Elsevier, London

    Google Scholar 

  • Gunduz T (1998) Susuz Ortam Reaksiyonları. Gazi Büro Kitabevi Tic. Ltd., Şti

    Google Scholar 

  • Gursoy-Kol O, Yuksek H, Islamoglu F (2012) In vitro antioxidant and acidic properties of novel 4-(5-methyl-2-thienylmethyleneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Synthesis and characterization. Rev Chim Buchar 63:1103–1111

    Google Scholar 

  • Hussain HH, Babic G, Durst T, Wright JS, Flueraru M, Chichirau A, Chepelev LL (2003) Development of novel antioxidants: design, synthesis, and reactivity. J Org Chem 68:7023–7032

    Article  CAS  PubMed  Google Scholar 

  • Ikizler AA, Un R (1979) Reactions of ester ethoxycarbonylhydrazones with some amine type compounds. [Chem. Abstr. 1981, 94, 15645d]. Chim Acta Turc 7:269–290

    CAS  Google Scholar 

  • Ikizler AA, Yuksek H (1993) Acetylation of 4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones. Org Prep Proced Int 25:99–105

    Article  CAS  Google Scholar 

  • Ikizler AA, Demirbas A, Johansson CB, Celik C, Serdar M, Yuksek H (1998) Synthesis and biological activity of some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Acta Pol Pharm 55:117–123

    CAS  PubMed  Google Scholar 

  • Iqbal AKM, Khan AY, Kalashetti MB, Belavagi NS, Gong YD, Khazi IAM (2012) Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring. Eur J Med Chem 53:308–315

    Article  Google Scholar 

  • Koca M, Servi S, Kirilmis C, Ahmedzade M, Kazaz C, Ozbek B, Otuk G (2005) Synthesis and antimicrobial activity of some novel derivatives of benzofuran: Part 1. Synthesis and antimicrobial activity of (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives. Eur J Med Chem 40:1351–1358

    Article  CAS  PubMed  Google Scholar 

  • Li ZY, Cao Y, Zhan P, Pannecouque C, Balzarini J, De Clercq E, Liu XY (2013) Synthesis and anti-HIV evaluation of novel 1,2,4-triazole derivatives as potential non-nucleoside HIV-1 reverse transcriptase inhibitors. Lett Drug Des Discov 10:27–34

    Article  Google Scholar 

  • McClements DJ, Decker EA (2000) Lipid oxidation in oil-in-water emulsions: impact of molecular environment on chemical reactions in heterogeneous food systems. J Food Sci 65:1270–1282

    Article  CAS  Google Scholar 

  • Meir S, Kanner J, Akiri B, Philosophhadas S (1995) Determination and involvement of aqueous reducing compounds in oxidative defense systems of various senescing leaves. J Agric Food Chem 43:1813–1819

    Article  CAS  Google Scholar 

  • Oyaizu M (1986) Studies on products of browning reaction prepared from glucosamine. Jpn J Nutr 44:307–316

    Article  CAS  Google Scholar 

  • Perez C, Pauli M, Bazerque P (1990) An antibiotic assay by the agar-well diffusion method. Acta Biol Med Exp 15:113–115

    Google Scholar 

  • Putun AE, Bereket G, Keskin E (1995) Potentiometric titrations of some 2-substituted 5-nitrobenzimidazole derivatives in nonaqueous solvent. J Chem Eng Data 40:221–224

    Article  Google Scholar 

  • Sahoo PK, Sharma R, Pattanayak P (2010) Synthesis and evaluation of 4-amino-5-phenyl-4H-[1,2,4]-triazole-3-thiol derivatives as antimicrobial agents. Med Chem Res 19:127–135

    Article  CAS  Google Scholar 

  • Siddiqui AA, Mishra R, Shaharvar M, Husain A, Rashid M, Pal P (2011) Triazole incorporated pyridazinones as a new class of antihypertensive agents: design, synthesis and in vivo screening. Bioorg Med Chem Lett 21:1023–1026

    Article  CAS  PubMed  Google Scholar 

  • Soares JR, Dinis TCP, Cunha AP, Almeida LM (1997) Antioxidant activities of some extracts of Thymus zygis. Free Radic Res 26:469–478

    Article  CAS  PubMed  Google Scholar 

  • Strlic M, Radovic T, Kolar J, Pihlar B (2002) Anti- and prooxidative properties of gallic acid in fenton-type systems. J Agric Food Chem 50:6313–6317

    Article  CAS  PubMed  Google Scholar 

  • Sujith KV, Kalluraya B, Adhikari A, Vijayanarayana K (2012) Microwave-mediated synthesis of triazolothiadiazoles as anti-inflammatory, analgesic, and anti-oxidant agents. Med Chem Res 21:543–551

    Article  CAS  Google Scholar 

  • Yamaguchi F, Ariga T, Yoshimura Y, Nakazawa H (2000) Antioxidative and anti-glycation activity of garcinol from Garcinia indica fruit rind. J Agric Food Chem 48:180–185

    Article  CAS  PubMed  Google Scholar 

  • Yildirim A, Mavi A, Kara AA (2001) Determination of antioxidant and antimicrobial activities of Rumex crispus L. extracts. J Agric Food Chem 49:4083–4089

    Article  CAS  PubMed  Google Scholar 

  • Yu D, Huiyuan G (2002) Synthesis and antibacterial activity of linezolid analogues. Bioorg Med Chem Lett 12:857–859

    Article  PubMed  Google Scholar 

  • Yuksek H, Gursoy-Kol O (2008) Preparation, characterization and potentiometric titrations of some new di-[3-(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl)-azomethinphenyl]isophtalate/terephtalate derivatives. Turk J Chem 32:773–784

    CAS  Google Scholar 

  • Yuksek H, Islamoglu F, Gursoy-Kol O, Bahceci S, Bekar M, Aksoy M (2011) In vitro antioxidant activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-ones having thiophene ring with their acidic properties. Eur J Chem 8:1734–1746

    CAS  Google Scholar 

  • Yuksek H, Akyildirim O, Yola ML, Gursoy-Kol O, Celebier M, Kart D (2013) Synthesis, in vitro antimicrobial and antioxidant activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives. Arch Pharm 346:470–480

    Article  Google Scholar 

Download references

Acknowledgments

The authors thank Dr. Zafer Ocak for the determination of pK a values and Dr. Mustafa Calapoglu for antioxidant activities.

Author information

Authors and Affiliations

  1. Education Faculty, Kafkas University, 36100, Kars, Turkey

    Ozlem Aktas-Yokus

  2. Department of Chemistry, Kafkas University, 36100, Kars, Turkey

    Haydar Yuksek & Ozlem Gursoy-Kol

  3. Department of Biology, Recep Tayyip Erdogan University, 53100, Rize, Turkey

    Sengul Alpay-Karaoglu

Authors
  1. Ozlem Aktas-Yokus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haydar Yuksek
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ozlem Gursoy-Kol
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sengul Alpay-Karaoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ozlem Gursoy-Kol.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Aktas-Yokus, O., Yuksek, H., Gursoy-Kol, O. et al. Synthesis and biological evaluation of new 1,2,4-triazole derivatives with their potentiometric titrations. Med Chem Res 24, 2813–2824 (2015). https://doi.org/10.1007/s00044-015-1334-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-015-1334-8

Keywords

Search

Navigation