• Mohit Kumar Department of Chemistry, Maharishi Markandeshwar University, Mullana (Ambala) 133207
  • Vinod Kumar Department of Chemistry, Maharishi Markandeshwar University, Mullana (Ambala) 133207, India
  • Vikas Beniwal Department of Biotechnology, Maharishi Markandeshwar University, Mullana (Ambala) 133207


Objective: To develop an easy and non toxic method for synthesis of some novel triazolotriazines via oxidative transformation of triazinylhydrazones using iodobenzene diacetate and to evaluate their DNA photocleavage potential.

Methods: A series nineteen triazin-3-yl moiety linked hydrazones of various aryl and heteroaryl aldehydes has been prepared which on treatment with iodobenzene diacetate in dichloromethane gave novel triazolo[3,4-c]triazine derivatives under mild reaction conditions. DNA photocleavage activity of all these compounds was performed using agarose gel electrophoresis.

Results: Synthesis of some novel triazolotriazines has been successively achieved and structures of compounds were established on the basis of FT-IR, 1H, 13C NMR and mass spectral data. Most of the compounds such as 4m-n, 4p-s, as well as 3b, 3d, 3e, 3h, 3p and 3q exhibited admirable DNA photocleavage potential.

Conclusion: The employed approach to afford triazolo[3,4-c]triazines only because the Dimorth rearrangement occurred under catalytic amount of base and acid etc. The results indicated that both triazolotriazines and triazinylhydrazones exhibited promising DNA photocleavage activity. Moreover, compounds containing phenyl ring with electron-releasing substituent attached to pyrazole nucleus possessed increased DNA photocleavage potential.


Keywords: Pyrazole, Triazole, Triazine, Hypervalent Iodine, DNA photocleavage.


Download data is not yet available.

Author Biographies

Mohit Kumar, Department of Chemistry, Maharishi Markandeshwar University, Mullana (Ambala) 133207
Vinod Kumar, Department of Chemistry, Maharishi Markandeshwar University, Mullana (Ambala) 133207, India
Vikas Beniwal, Department of Biotechnology, Maharishi Markandeshwar University, Mullana (Ambala) 133207


1. Negwer M. Organic-chemical drugs and their synonyms: an international survey. Akademie Verlag: Berlin Publishers; 1987.
2. Sidwell RW, Dixon GJ, Sellers SM, Schabel FM. In vivo antiviral properties of biologically active compounds. Appl Microbiol 1968;16:370-92.
3. Falke D, Rada B. 6-Azauridine as an inhibitor of the synthesis of herpesvirus hominis. Acta Virol 1976;14:115-23.
4. Wrobleski ST, Lin S, Jr JH, Wu H, Pitt S, Shen DR, et al. Synthesis and SAR of new pyrrolo[2,1-f][1,2,4]triazines as potent p38a MAP kinase inhibitors. Bioorg Med Chem Lett 2008;18:2739-44.
5. El-Gendy Z, Morsy JM, Allimony HA, Ali WRAM, Abdel-Rahman RM. Synthesis of heterobicyclic nitrogen systems bearing the 1,2,4-triazine moiety as anti-HIV and anticancer drugs, Part III. Pharmazie 2001;56:376-83.
6. Abdel-Rahman RM, Morsy JM, El-Edfawy S, Amine HA. Synthesis of heterobicyclic nitrogen systems bearing the 1,2,4-triazine moiety as anti-HIV and anticancer drugs: Part I. Pharmazie 1999;54:667-83.
7. Abdel-Rahman RM, Morsy JM, El-Edfawy S, Amine HA. Synthesis of heterobicyclic nitrogen systems bearing the 1,2,4-triazine moiety as anti-HIV and anticancer drugs: Part I. Pharmazie 1999;54:347-51.
8. Sztanke K, Pasternak K, Sztanke M, Kandefer-Szerszen M, Kozioł AE, Dybała I. Crystal structure, antitumour and antimetastatic activities of disubstituted fused 1,2,4-triazinones. Bioorg Med Chem Lett 2009;19:5095-100.
9. Sztanke K, Rzymowska J, Niemczyk M, Dybała I, Kozioł AE. Synthesis, crystal structure and anticancer activity of novel derivatives of ethyl 1-(4-oxo-8-aryl-4,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazin-3-yl)formate. Eur J Med Chem 2006;41:539-47.
10. Ali TES. Synthesis of some novel pyrazolo[3,4-b]pyridine and pyrazolo[3,4-d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents. Eur J Med Chem 2009;44:4385-92.
11. Dolzhenko AV, Tan BJ, Dolzhenko AV, Chiu GNC, Chui WK. Synthesis and biological activity of fluorinated 7-aryl-2-pyridyl-6,7-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazin-5-amines. J Fluorine Chem 2008;129:429-34.
12. EL-Massry AM, Asal AM, Khattab SN, Haiba NS, Awney HA, Helmy M, et al. Synthesis and structure elucidation of novel fused 1,2,4-triazine derivatives as potent inhibitors targeting CYP1A1 activity. Bioorg Med Chem 2012;20:2624-37.
13. Gupta GK, Saini V, Khare R, Kumar V. 1, 4-Diaryl-2-mercaptoimidazoles as a novel class of antimicrobial agents: Design, synthesis and computational studies. Med Chem Res 2014;23:4209-20.
14. Gupta GK, Kumar V. Pyrazoles as potential anti-obesity agents: a review, Res J Chem Environ 2011;15(3): 90-103.
15. Kumar V, Kaur K, Gupta GK, Gupta AK, Kumar S. Developments in synthesis of the anti-inflammatory drug, Celecoxib: a review. Recent Pat Inflammation Allergy Drug Discovery 2013;7:124-34.
16. Kumar V, Kaur K, Sharma AK, Gupta AK. Pyrazole containing natural product: synthetic preview and biological significance. Eur J Med Chem 2013;69:735-53.
17. Kumar V, Kaur K, Gupta GK, Sharma AK. Isoxazoline containing natural products as anticancer agents: a review. Eur J Med Chem 2014;77:121-33.
18. Bektas H, Karaali N, Sahin D, Demirbas A, Karaoglu SA, Demirbas N. Synthesis and antimicrobial activities of some new 1,2,4-triazole derivatives. Molecule 2010;15:2427-38.
19. Kumar R, Nair RR, Dhiman SS, Sharma J, Prakash O. Organoioine (III)-mediated synthesis of 3-aryl/heteroaryl-5,7-dimethyl-1,2,4-triazolo[4,3-c]pyrimidines as antibacterial agents. Eur J Med Chem 2009;44:2260-4.
20. Sztanke K, Tuzimski T, Rzymowska J, Pasternak K, Szerszen MK. Synthesis, determination of the lipophilicity, anticancer and antimicrobial properties of some fused 1,2,4-triazole derivatives. Eur J Med Chem 2008;43:404-19.
21. Mohareb RM, El-Sayed NNE, Abdelaziz MA. Uses of cyanoacetylhydrazine in heterocyclic synthesis: novel synthesis of pyrazole derivatives with anti-tumor activities. Molecule 2012;17:8449-63.
22. Ravala JP, Shaha AB, Patela NH. Synthesis and anti‐tubercular activity of novel pyrazol‐5(H)‐one derivatives. Eur J Med Chem 2011;2:238-42.
23. Shiradkar M, Kumar GVS, Desai V, Tatikonda S, Akula KC, Shah R. Clubbed triazole: a novel approach to antitubercular drugs. Eur J Med Chem 2007;42:807-16.
24. Al-Ayed AS. Synthesis of new substituted chromen[4,3-c]pyrazol-4-ones and their antioxidant activities. Molecule 2011;16:10292-302.
25. Mariappan G, Saha BP, Sutharson L, Haldar A. Synthesis and bioactivity evaluation of pyrazoline derivatives. Indian J Chem 2010;49B: 1671-4.
26. Aziz MA, Rohma GE, Hassan AA. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activity. Eur J Med Chem 2009;44:3480-7.
27. Yu LT, Ho MT, Chang CY, Yang TK. Asymmetric zinc-reformatsky reaction of evans chiral imide with acetophenones and its application to the stereoselective synthesis of triazole antifungal agents. Tetrahedron Asymmetr 2007;18:949-62.
28. Gupta A, Unadkat JD, Mao Q. Interactions of azole antifungal agents with the human breast cancer resistance protein. J Pharm Sci 2007;96:3226-35.
29. Ashok M, Holla BS, Poojary B. Convenient one pot synthesis and antimicrobial evaluation of some new mannich bases carrying 4-methylthiobenzyl moiety. Eur J Med Chem 2007;42:1095-101.
30. Raman N, Raja SJJ. DNA cleavage, structural elucidation and anti-microbial studies of three novel mixed ligand Schiff base complexes of copper (II). Serb Chem Soc 2007;72:983-92.
31. Kurdekar GS, Puttanagouda SM, Kulkarni NV, et al. Synthesis, characterization, antibiogram and DNA binding studies of novel Co(II), Ni(II), Cu(II), and Zn(II) complexes of Schiff base ligands with quinoline core. Med Chem Res 2011;20:421-9.
32. Aggarwal R, Sumran G, Kumar V, Mittal A. Copper (II) chloride mediated synthesis and DNA photocleavage activity of 1-aryl/heteroaryl-4-substituted-1,2,4-triazolo[4,3-a]quinoxalines. Eur J Med Chem 2011;46:6083-8.
33. Manfredini S, Vicentini CB, Manfrini M, et al. Pyrazolo-triazoles as light activable DNA cleaving agents. Bioorg Med Chem 2000;8:2343-6.
34. Kulkarni AKD, Patil SA, Naik VH, Badam PS. DNA cleavage and antimicrobial investigation of Co(II), Ni(II), and Cu(II) complexes with triazole Schiff bases: synthesis and spectral characterization. Med Chem Res 2011;20:346-54.
35. Hanumanagoud H, Basavaraja KM. Synthesis, antibacterial, antifungal activity and DNA cleavage study of 3-(7-methoxy-benzofuran-2-yl)-5-aryl-4H-[1,2,4]triazoles. J Chem Pharm Res 2012;4:5165-71.
36. Taj TR, Kamble R, Badami BV. Synthetic utility of sydnones: Synthesis of pyrazolines derivatized with 1,2,4-triazoles as antihyperglymic, antioxidant agents and their DNA cleavage study. Med Chem Res 2012;21:3709-19.
37. Kumar V, Kaur K, Karelia DN, Beniwal V, Gupta GK, Sharma AK, Gupta AK. Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: Antibacterial, DNA photocleavage, and anticancer activities. Eur J Med Chem 2014;81:267-76.
38. Tegginamath G, Kamble RR, Kattimani PP, Margankop SB. Synthesis of 3-aryl-4-({2-[4-(6-substituted-coumarin-3-yl)-1,3-thiazol-2-yl]hydrazinylidene}methyl/ethyl)-sydnones using silica sulfuric acid and their antidiabetic, DNA cleavage activity. Arab J Chem 2011;doi: 10.1016/j. arabjc. 2011.04.006.(Article increagd).
39. Aggarwal R, Kumar R, Kumar V. A facile and rapid one-pot synthesis of 1,4-diaryl-2-mercaptoimidazoles under solvent-free Conditions. J Sulfur Chem 2007;28:617-23.
40. Kumar P. An environmentally benign and solvent-free synthesis of 3-aryl[1,2,4]triazolo[4,3-a]pyridines and 1-aryl-5-methyl[1,2,4]triazolo[4,3-a]quinolines using phenyliodine bis(trifl-uoroacetate) or iodobenzene diacetate. J Heterocycl Chem 2012;47:1237-43.
41. Zhdankin VV. Hypervalent iodine (III) reagents in organic synthesis. Arkivoc 2009;1:1-62.
42. Braibante MEF, Braibante HTS, Uliana MP, Costa CC, Spenazzatto M. The use of benzil to obtain functionalized N-heterocycles. J Braz Chem Soc 2008;19:909-13.
43. Mullick P, Khan S, Begum T, Verma S, Kaushik D, Alam O. Synthesis of 1,2,4-triazine derivatives as potential anti-anxiety and anti-inflammatory agents. Acta Poloniae Pharmaceutica Drug Res 2009;66:379-85.
44. Rahimizadeh M, Bakavoli M, Gordi Z, Seyedi SM. Synthesis of Two New Heterocyclic Systems: furo[3',2':5,6]pyrimido[2,1-c][1,2,4]triazines and furo[3,2-e][1,2,3,4]tetrazolo[1,5-a]pyrimidine. J Iran Chem Soc 2011;8:1135-8.
45. Rajput AP, Rajput SS. A novel method for the synthesis of formyl pyrazoles using vilsmeier-haack reaction. Int J Pharm Pharm Sci 2011;3:346-51.
46. Prakash O, Hussain K, Aneja DK, Sharma C, Aneja KR. A facile iodine (III)-mediated synthesis of 3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridines via oxidation of 2-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-1-(pyridin-2-yl)hydrazines and their antimicrobial evaluations. Org Med Chem Lett 2011;1:1-9.
724 Views | 718 Downloads
How to Cite
Kumar, M., V. Kumar, and V. Beniwal. “SYNTHESIS OF SOME NOVEL 3,5,6-TRISUBSTITUTED-[1,2,4]TRIAZOLO[3,4-c][1,2,4] TRIAZINESAS DNA PHOTOCLEAVING AGENTS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 9, 1, pp. 376-83,
Original Article(s)