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Abstract

In this work, novel organic based compounds 1,2,4-triazine derivatives were synthesized and their antimicrobial and anticancer activities were investigated. A new series of 1,2,4-triazine derivatives (IVa-c) containing pyridine ring were prepared via reaction of N-benzoyl glycine with aromatic aldehydes in presence of fused sodium acetate and acetic anhydride to give oxazolinone derivatives (IIa-c), followed by condensation of compound II with nicotinic acid hydrazide in glacial acetic acid. 3-Substituted pyridinium acetate (Va-c) was obtained via acetylation of compounds (IVa-c) with acetic anhydride. The structures of the synthesized 1,2,4-triazine derivatives (IV and V) were confirmed by IR, 1H NMR, 13C NMR, MS and elemental analysis. Antimicrobial and cytotoxicity activities of some synthesized compounds have been investigated. The previous compounds, selected as potential agent′s hepatocellular carcinoma were then evaluated in vitro for their biological activity on HCC-derived cell lines. The compounds IVa, Va and Vb show a promising inhibitory growth efficiency (IC50 4.30, 4.70 and 4.00 μM) with compared standard antitumor drug (IC50 4.60 μM).

Keywords

Pyridoyl moiety Antimicrobial activity Cytotoxicity activity 1,2,4-Triazines

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A. Zein, M., & I. El-Shenawy, A. (2018). Synthesis of Some New 1,2,4-Triazines Bearing Pyridoyl Moiety as Potential Antimicrobial and Anticancer Agents. Asian Journal of Organic & Medicinal Chemistry, 3(4), 181–186. https://doi.org/10.14233/ajomc.2018.AJOMC-P153
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References

  1. I. Vujasinovic, A. Paravic-Radièevic, K. Mlinaric-Majerski, K. Brajša and B. Bertoša, Synthesis and Biological Validation of Novel Pyrazole Derivatives with Anticancer Activity Guided by 3D-QSAR Analysis, Bioorg. Med. Chem., 20, 2101 (2012); https://doi.org/10.1016/j.bmc.2012.01.032.
  2. P. Pevarello, D. Fancelli, A. Vulpetti, R. Amici, M. Villa, V. Pittalà, P. Vianello, A. Cameron, M. Ciomei, C. Mercurio, J.R. Bischoff, F. Roletto, M. Varasi and M.G. Brasca, 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]-pyrazoles: A New Class of CDK2 Inhibitors, Bioorg. Med. Chem. Lett., 16, 1084 (2006); https://doi.org/10.1016/j.bmcl.2005.10.071.
  3. N.W. Gibson, L.G. Erickson and J.A. Hickman, Effects of the Antitumor Agent 8-Carbamoyl-3-(2-chloroethyl)imidaz[5,1-d]-1,2,3,5-tetrazin-4(3H)-one on the DNA of mouse L1210 cells, Cancer Res., 44, 1767 (1984).
  4. D.D. Pilch, M.A. Kirolos, X. Liu, G.E. Plum and K.J. Breslauer, Berenil [1,3-Bis(4’-amidinophenyl)triazene] Binding to DNA Duplexes and to a RNA Duplex: Evidence for Both Intercalative and Minor Groove Binding Properties, Biochem. Pharmacol., 34, 9962 (1995).
  5. B.J. Jean-Claude, A. Mustafa, Z. Damian, J. De Marte, D.E. Vasilescu, R. Yen, T.H. Chan and B. Leyland-Jones, Cytokinetics of a Novel 1,2,3-Triazene-Containing Heterocycle, 8-Nitro-3-methyl-benzo-1,2,3,5-tetrazepin-4(3H)-one (NIME), in the Human Epithelial Ovarian Cancer Cell Line OVCAR-3, Biochem. Pharmacol., 57, 753 (1999); https://doi.org/10.1016/S0006-2952(98)00345-1.
  6. R.H. Smith, D.A. Scudiero and C.J. Michejda, 1,3-Dialkyl-3-Acyltria-zenes, A novel Class of Antineoplastic Alkylating Agents, J. Med. Chem., 33, 2579 (1990); https://doi.org/10.1021/jm00171a036.
  7. S. Unsalan and S. Rollas, Synthesis and Primary Cytotoxicity Evaluation of New Diaryltriazenes, Indian J. Chem., 46B, 185 (2007).
  8. A. Kumar, S.K. Mukerjee and S.K. Bhattacharya, Anticonvulsant and Monoamine Oxidase Inhibitory Activities of Some Triazene N1-Oxides, Pharm. Res., 2, 49 (1985); https://doi.org/10.1023/A:1016374224529.
  9. A. Katsoulas, Z. Rachid, F. Brahimi, J. Mcnamee and B.J. Jean-Claude, Engineering 3-Alkyltriazenes to Block bcr-abl Kinase: A Novel Strategy for the Therapy of Advanced bcr-abl Expressing Leukemias, Leuk. Res., 29, 49 (2005).
  10. K. Seiter, D. Liu, T. Loughran, A. Siddiqui, P. Baskind and T. Ahmed, Phase I Study of Temozolomide in Relapsed/Refractory Acute Leukemia, Clin. Oncol., 20, 3249 (2002); https://doi.org/10.1200/JCO.2002.01.030.
  11. B.T. Collins, S. Vahdat, K. Erickson, S.P. Collins, S. Suy, X. Yu, Y. Zhang, D. Subramaniam, C.A. Reichner, I. Sarikaya, G. Esposito, S. Yousefi, C. Jamis-Dow, F. Banovac and E.D. Anderson, Radical Cyberknife Radiosurgery with Tumor Tracking: An Effective Treatment for Inoperable Small Peripheral Stage I Non-Small Cell Lung Cancer, J. Hematol. Oncol., 2, 1 (2009); https://doi.org/10.1186/1756-8722-2-1.
  12. I. Manolov, H.J. Machulla and G. Momekov, Synthesis, Physicochemical Characterization and Preliminary Pharmacological in vitro Evaluation of Two Novel Cytotoxic Benzophenone-Linked 3,3-Dimethyltriazenes, Pharmazie, 61, 511 (2006).
  13. B.S. Dawane, S.G. Konda, G.G. Mandawad and B.M. Shaikh, Poly-(ethylene glycol) (PEG-400) as an Alternative Reaction Solvent for the Synthesis of Some New 1-(4-(4¢-Chlorophenyl)-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1H-imidazol-5yl)-2-pyrazolines and their in vitro Antimi-crobial Evaluation, Eur. J. Med. Chem., 45, 387 (2010); https://doi.org/10.1016/j.ejmech.2009.10.015.
  14. B.S. Dawane, S.N. Kadam and B.M. Shaikh, An Efficient Synthesis of 1, 2, 4-triazine Derivatives and their in vitro Antimicrobial Activity, Der Pharm. Lett., 2, 126 (2010).
  15. M. Abd El-Moneim, J.A. Hasanen, I.M. El-Deen and W. Abd El-Fattah, Synthesis of Fused 1,2,4-Triazines as Potential Antimicrobial and Anti-tumor Agents, Res. Chem. Intermed., 41, 3543 (2015); https://doi.org/10.1007/s11164-013-1470-z.
  16. M.A. El-Latif Zein and A.I. El-Shenawy, An Efficient Synthesis of 1,2,4-Triazine-6-one Derivatives and their in vitro Anticancer Activity, Int. J. Pharmacol., 12, 188 (2016); https://doi.org/10.3923/ijp.2016.188.194.
  17. I.M. El-Deen, Use of 3-(2¢-Formyl-1¢-chlorovinyl)coumarin in the Syntheses of Pyrazol, Salicylaldazine and Pyrimidine Derivatives, Chin. J. Chem., 17, 391 (1999); https://doi.org/10.1002/cjoc.19990170412.
  18. A.I. El-Shenawy, Synthesis and in vitro Antimicrobial and Antitumor Activity of Some Nitrogen Heterocycles, J. Russian Bioorg. Chem., 42, 100 (2016); https://doi.org/10.1134/S1068162016010040.
  19. H.A.H. Elshemy, E.K.A. Abdelall, A.A. Azouz, A. Moawad, W.A.M. Ali and N.M. Safwat, Synthesis, Anti-Inflammatory, Cyclooxygenases Inhibitions Assays and Histopathological Study of Poly-Substituted 1,3,5-Triazines: Confirmation of Regiospecific Pyrazole Cyclization By HMBC, Eur. J. Med. Chem., 127, 10 (2017); https://doi.org/10.1016/j.ejmech.2016.12.030.
  20. X. Zhou, K. Lin, X. Ma, W.-K. Chui and W. Zhou, Design, Synthesis, Docking Studies and Biological Evaluation of Novel Dihydro-1,3,5-Triazines as Human DHFR Inhibitors, Eur. J. Med. Chem., 1279 (2017); https://doi.org/10.1016/j.ejmech.2016.11.010.
  21. R.V. Patel, P. Kumari, D.P. Rajani and K.H. Chikhalia, Synthesis and Studies of Novel 2-(4-Cyano-3-Trifluoromethylphenylamino)-4-(Quinoline-4-yloxy)-6-(Piperazinyl/Piperidinyl)-S-Triazines as Potential Antimic-robial, Antimycobacterial and Anticancer Agents, Eur. J. Med. Chem., 46, 4354 (2011); https://doi.org/10.1016/j.ejmech.2011.07.006.
  22. C. Perez, M. Pauli and P. Bazerque, An Antibiotic Assay by Agar Well Diffusion Method, Acta Biol. Med. Exp., 15, 113 (1990).
  23. NCCLS, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria, which Grows Aerobically, Approved Standard M7- A5, NCCLS, P.A. Villanova, edn 5 (2000).
  24. T.J. Mosmann, Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays, Immuno-methods, 65, 55 (1983).
  25. V. Gangadevi and J. Muthumary, Preliminary Studies on Cytotoxic Effect of Fungal Taxol on Cancer Cell Lines, Afr. J. Biotechnol., 6, 1382 (2007); https://doi.org/10.5897/AJB2007.000-2194.