Login Register Cart 0
Generic placeholder image

Current Drug Discovery Technologies

Editor-in-Chief

ISSN (Print): 1570-1638
ISSN (Online): 1875-6220

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

In-vitro Evaluation of Triazine Scaffold for Anticancer Drug Development: A Review

Author(s): Pragya Dubey, Dharam Pal Pathak, Faraat Ali*, Garima Chauhan and Vivekanandan Kalaiselvan

Volume 21, Issue 2, 2024

Published on: 01 September, 2023

Article ID: e170723218813 Pages: 16

DOI: 10.2174/1570163820666230717161610

Price: $65

conference banner
Abstract

Introduction: The widespread importance of the synthesis and modification of anticancer agents has given rise to many numbers of medicinal chemistry programs. In this regard, triazine derivatives have attracted attention due to their remarkable activity against a wide range of cancer cells. This evaluation covers work reports to define the anticancer activity, the most active synthesized compound for the target, the SAR and, when described, the probable MOA besides similarly considered to deliver complete and target-pointed data for the development of types of anti-tumour medicines of triazine derivatives. Triazine scaffold for the development of anticancer analogues. Triazine can also relate to numerous beneficial targets, and their analogues have auspicious in-vitro and in-vivo anti-tumour activity. Fused molecules can improve efficacy, and drug resistance and diminish side effects, and numerous hybrid molecules are beneath diverse stages of clinical trials, so hybrid derivatives of triazine may offer valuable therapeutic involvement for the dealing of tumours.

Objective: The objective of the recent review was to summarize the recent reports on triazine as well as its analogues with respect to its anticancer therapeutic potential.

Conclusion: The content of the review would be helpful to update the researchers working towards the synthesis and designing of new molecules for the treatment of various types of cancer disease with the recent molecules that have been produced from the triazine scaffold. Triazine scaffolds based on 1,3,5-triazine considerably boost molecular diversity levels and enable covering chemical space in key medicinal chemistry fields.

Graphical Abstract

[1]
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65(1): 5-29.
[http://dx.doi.org/10.3322/caac.21254] [PMID: 25559415]
[2]
Novotny L, Szekeres T. Cancer therapy: new targets for chemotherapy. Hematology 2003; 8(3): 129-37.
[http://dx.doi.org/10.1080/1024533031000112257] [PMID: 12745645]
[3]
Jung KH, Park BH, Hong SS. Progress in cancer therapy targeting c-Met signaling pathway. Arch Pharm Res 2012; 35(4): 595-604.
[http://dx.doi.org/10.1007/s12272-012-0402-6] [PMID: 22553051]
[4]
Sridhar A, Saremy S, Bhattacharjee B. Elucidation of molecular targets of bioactive principles of black cumin relevant to its anti-tumour functionality - An in silico target fishing approach. Bioinformation 2014; 10(11): 684-8.
[http://dx.doi.org/10.6026/97320630010684] [PMID: 25512684]
[5]
Cereto-Massagué A, Ojeda MJ, Valls C, Mulero M, Pujadas G, Garcia-Vallve S. Tools for in silico target fishing. Methods 2015; 71: 98-103.
[http://dx.doi.org/10.1016/j.ymeth.2014.09.006] [PMID: 25277948]
[6]
Dbm V. In silico screening of secondary metabolites derived from marine fungi for anticancer study. J Adv Bioinform Appl Res 2014; 5(2): 78-82.
[7]
Peach ML, Nicklaus MC. Combining docking with pharmacophore filtering for improved virtual screening. J Cheminform 2009; 1(1): 6.
[http://dx.doi.org/10.1186/1758-2946-1-6] [PMID: 20298524]
[8]
Thangapandian S, John S, Sakkiah S, Lee KW. Ligand and structure based pharmacophore modeling to facilitate novel histone deacetylase 8 inhibitor design. Eur J Med Chem 2010; 45(10): 4409-17.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.024] [PMID: 20656379]
[9]
Koutsoukas A, Simms B, Kirchmair J, et al. From in silico target prediction to multi-target drug design: Current databases, methods and applications. J Proteomics 2011; 74(12): 2554-74.
[http://dx.doi.org/10.1016/j.jprot.2011.05.011] [PMID: 21621023]
[10]
Wang L, Xie XQ. Computational target fishing: what should chemogenomics researchers expect for the future of in silico drug design and discovery? Future Med Chem 2014; 6(3): 247-9.
[http://dx.doi.org/10.4155/fmc.14.5] [PMID: 24575960]
[11]
Liu X, Ouyang S, Yu B, et al. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res 2010; 38(Web Server issue)(Suppl. 2): W609-14.
[http://dx.doi.org/10.1093/nar/gkq300] [PMID: 20430828]
[12]
Bahar AA, Liu Z, Garafalo M, Kallenbach N, Ren D. Controlling persister and biofilm cells of gram-negative bacteria with a new 1, 3, 5-triazine derivative. Pharmaceuticals (Basel) 2015; 8(4): 696-710.
[http://dx.doi.org/10.3390/ph8040696] [PMID: 26473884]
[13]
Mibu N, Yokomizo K, Aki H, et al. Synthesis and antiviral evaluation of some C3-symmetrical trialkoxy-substituted 1, 3, 5-triazines and their molecular geometry. Chem Pharm Bull (Tokyo) 2015; 63(11): 935-44.
[http://dx.doi.org/10.1248/cpb.c15-00309] [PMID: 26521858]
[14]
Zacharie B, Abbott SD, Bienvenu JF, et al. 2,4,6-trisubstituted triazines as protein a mimetics for the treatment of autoimmune diseases. J Med Chem 2010; 53(3): 1138-45.
[http://dx.doi.org/10.1021/jm901403r] [PMID: 20047277]
[15]
Liu B, Sun T, Zhou Z, Du L. A systematic review on antitumor agents with 1, 3, 5-triazines. Med Chem 2015; 5(3): 131-48.
[http://dx.doi.org/10.4172/21610444.1000255]
[16]
Singla P, Luxami V, Paul K. Triazine as a promising scaffold for its versatile biological behavior. Eur J Med Chem 2015; 102: 39-57.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.037] [PMID: 26241876]
[17]
Lim FPL, Dolzhenko AV. 1,3,5-Triazine-based analogues of purine: From isosteres to privileged scaffolds in medicinal chemistry. Eur J Med Chem 2014; 85: 371-90.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.112] [PMID: 25105925]
[18]
Patel R, Keum YS, Park S. Medicinal chemistry discoveries among 1,3,5-triazines: Recent advances (2000-2013) as antimicrobial, anti-TB, anti-HIV and antimalarials. Mini Rev Med Chem 2014; 14(9): 768-89.
[http://dx.doi.org/10.2174/1389557514666140622205904] [PMID: 24958216]
[19]
Tretamine. Available From: https://go.drugbank.com/drugs/DB14031 (assessed on 09/12/2020).
[20]
Altretamine. Available From: https://go.drugbank.com/drugs/DB00488 (assessed on 09/12/2020).
[21]
Azacitidine. Available From: https://go.drugbank.com/drugs/DB00928 (assessed on 09/12/2020).
[22]
Enasidenib. Available From: https://go.drugbank.com/drugs/DB13874 (assessed on 09/12/2020).
[23]
Decitabine. Available From: https://go.drugbank.com/drugs/DB01262 (assessed on 09/12/2020).
[24]
Gedatolisib. Available From: https://go.drugbank.com/drugs/DB11896 (assessed on 09/12/2020).
[25]
Lamotrigine. Available From: https://go.drugbank.com/drugs/DB00555 (assessed on 09/12/2020).
[26]
Tirapazamine. Available From: https://go.drugbank.com/drugs/DB04858 (assessed on 09/12/2020).
[27]
Lolak N, Akocak S, Bua S, Sanku RKK, Supuran CT. Discovery of new ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as carbonic anhydrase I, II, IX and XII inhibitors. Bioorg Med Chem 2019; 27(8): 1588-94.
[http://dx.doi.org/10.1016/j.bmc.2019.03.001] [PMID: 30846402]
[28]
Shi W, Qiang H, Huang D, Bi X, Huang W, Qian H. Exploration of novel pyrrolo[2,1-f][1,2,4]triazine derivatives with improved anticancer efficacy as dual inhibitors of c-Met/VEGFR-2. Eur J Med Chem 2018; 158: 814-31.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.050] [PMID: 30248654]
[29]
Moreno L, Quiroga J, Abonia R, Ramírez-Prada J, Insuasty B. Synthesis of new 1, 3, 5-triazine-based 2-pyrazolines as potential anticancer agents. Molecules 2018; 23(8): 1956.
[http://dx.doi.org/10.3390/molecules23081956] [PMID: 30082588]
[30]
El-Wakil MH, Ashour HM, Saudi MN, Hassan AM, Labouta IM. Design, synthesis and molecular modeling studies of new series of antitumor 1,2,4-triazines with potential c-Met kinase inhibitory activity. Bioorg Chem 2018; 76: 154-65.
[http://dx.doi.org/10.1016/j.bioorg.2017.11.006] [PMID: 29175587]
[31]
Fu DJ, Song J, Hou YH, et al. Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers. Eur J Med Chem 2017; 138: 1076-88.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.011] [PMID: 28763643]
[32]
Narva S, Chitti S, Amaroju S, et al. Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors. Bioorg Med Chem Lett 2017; 27(16): 3794-801.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.060] [PMID: 28684120]
[33]
Nasr T, Bondock S, Youns M, Fayad W, Zaghary W. Synthesis, antitumor evaluation and microarray study of some new pyrazolo[3,4- d][1,2,3]triazine derivatives. Eur J Med Chem 2017; 141: 603-14.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.016] [PMID: 29107422]
[34]
Shen F, Ou ZB, Liu YJ, et al. Two Cu(II) complexes containing 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and amino acids: Synthesis, crystal structures, DNA/HSA binding, molecular docking, and in-vitro cytotoxicity studies. Inorg Chim Acta 2017; 465: 1-13.
[http://dx.doi.org/10.1016/j.ica.2017.05.030]
[35]
Fan YB, Li K, Huang M, et al. Design and synthesis of substituted pyrido[3,2-d]-1,2,3-triazines as potential Pim-1 inhibitors. Bioorg Med Chem Lett 2016; 26(4): 1224-8.
[http://dx.doi.org/10.1016/j.bmcl.2016.01.032] [PMID: 26804231]
[36]
Kothayer H, Spencer SM, Tripathi K, Westwell AD, Palle K. Synthesis and in-vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors. Bioorg Med Chem Lett 2016; 26(8): 2030-4.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.085] [PMID: 26965855]
[37]
Singla P, Luxami V, Paul K. Synthesis and in-vitro evaluation of novel triazine analogues as anticancer agents and their interaction studies with bovine serum albumin. Eur J Med Chem 2016; 117: 59-69.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.088] [PMID: 27089212]
[38]
Wang G, Peng Z, Wang J, Li X, Li J. Synthesis, in-vitro evaluation and molecular docking studies of novel triazine-triazole derivatives as potential α-glucosidase inhibitors. Eur J Med Chem 2017; 125: 423-9.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.067] [PMID: 27689725]
[39]
Mojzych M, Ceruso M, Bielawska A, Bielawski K, Fornal E, Supuran CT. New pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors. Bioorg Med Chem 2015; 23(13): 3674-80.
[http://dx.doi.org/10.1016/j.bmc.2015.04.011] [PMID: 25921266]
[40]
Singla P, Luxami V, Paul K. Triazine–benzimidazole hybrids: Anticancer activity, DNA interaction and dihydrofolate reductase inhibitors. Bioorg Med Chem 2015; 23(8): 1691-700.
[http://dx.doi.org/10.1016/j.bmc.2015.03.012] [PMID: 25792141]
[41]
Patel AB, Chikhalia KH, Kumari P. An efficient synthesis of new thiazolidin-4-one fused s-triazines as potential antimicrobial and anticancer agents. J Saudi Chem Soc 2014; 18(5): 646-56.
[http://dx.doi.org/10.1016/j.jscs.2014.02.002]
[42]
Yurttaş L, Demirayak Ş Ilgın S, Atlı Ö. In-vitro antitumor activity evaluation of some 1,2,4-triazine derivatives bearing piperazine amide moiety against breast cancer cells. Bioorg Med Chem 2014; 22(22): 6313-23.
[http://dx.doi.org/10.1016/j.bmc.2014.10.002] [PMID: 25438754]
[43]
Pogorelčnik B, Brvar M, Zajc I, Filipič M, Solmajer T, Perdih A. Monocyclic 4-amino-6-(phenylamino)-1,3,5-triazines as inhibitors of human DNA topoisomerase IIα. Bioorg Med Chem Lett 2014; 24(24): 5762-8.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.042] [PMID: 25453816]
[44]
Kang SM, Lee J, Jin JH, et al. Synthesis and PGE2 production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells. Bioorg Med Chem Lett 2014; 24(23): 5418-22.
[http://dx.doi.org/10.1016/j.bmcl.2014.10.031] [PMID: 25453800]
[45]
Mojzych M, Bielawska A, Bielawski K, Ceruso M, Supuran CT. Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity. Bioorg Med Chem 2014; 22(9): 2643-7.
[http://dx.doi.org/10.1016/j.bmc.2014.03.029] [PMID: 24713308]
[46]
Bera H, Lee MH, Sun L, Dolzhenko AV, Chui WK. Synthesis, anti-thymidine phosphorylase activity and molecular docking of 5-thioxo-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-ones. Bioorg Chem 2013; 50: 34-40.
[http://dx.doi.org/10.1016/j.bioorg.2013.07.004] [PMID: 23968897]
[47]
Dao P, Jarray R, Le Coq J, et al. Synthesis of novel diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity. Bioorg Med Chem Lett 2013; 23(16): 4552-6.
[http://dx.doi.org/10.1016/j.bmcl.2013.06.038] [PMID: 23845217]
[48]
Khoshneviszadeh M, Ghahremani MH, Foroumadi A, et al. Design, synthesis and biological evaluation of novel anti-cytokine 1, 2, 4-triazine derivatives. Bioorganic & medicinal chemistry 2013; 21(21): 6708-17.
[49]
Kothayer H, Elshanawani AA, Abu Kull ME, et al. Design, synthesis and in-vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides. Bioorg Med Chem Lett 2013; 23(24): 6886-9.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.087] [PMID: 24153206]
[50]
EL Massry AM, Asal AM, Khattab SN, 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(8): 2624-37.
[http://dx.doi.org/10.1016/j.bmc.2012.02.041] [PMID: 22414679]
[51]
Sączewski F, Bułakowska A, Bednarski P, Grunert R. Synthesis, structure and anticancer activity of novel 2,4-diamino-1,3,5-triazine derivatives. Eur J Med Chem 2006; 41(2): 219-25.
[http://dx.doi.org/10.1016/j.ejmech.2005.10.013] [PMID: 16377034]
[52]
Balahaa MF, El-Hamamsyb MH, El-Dinc NA, El-Mahdyd NA. Synthesis, evaluation and docking study of 1, 3, 5-triazine derivatives as cytotoxic agents against lung cancer. J Appl Pharm Sci 2016; 6(4): 28-45.
[http://dx.doi.org/10.7324/JAPS.2016.60405]
[53]
Huang Q, Fu Q, Liu Y, et al. Design, synthesis and anticancer activity of novel 6-(aminophenyl)-2,4-bismorpholino-1,3,5-triazine derivatives bearing arylmethylene hydrazine moiety. Chem Res Chin Univ 2014; 30(2): 257-65.
[http://dx.doi.org/10.1007/s40242-014-3253-5]
[54]
Sączewski F, Bułakowska A. Synthesis, structure and anticancer activity of novel alkenyl-1,3,5-triazine derivatives. Eur J Med Chem 2006; 41(5): 611-5.
[http://dx.doi.org/10.1016/j.ejmech.2005.12.012] [PMID: 16540207]
[55]
Yan W, Zhao Y, He J. Anti breast cancer activity of selected 1,3,5 triazines via modulation of EGFR TK. Mol Med Rep 2018; 18(5): 4175-84.
[http://dx.doi.org/10.3892/mmr.2018.9426] [PMID: 30152850]
[56]
Srivastava JK, Pillai GG, Bhat HR, Verma A, Singh UP. Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase. Sci Rep 2017; 7(1): 5851.
[http://dx.doi.org/10.1038/s41598-017-05934-5] [PMID: 28724908]
[57]
Wróbel A, Kolesińska B, Frączyk J, et al. Synthesis and cellular effects of novel 1,3,5-triazine derivatives in DLD and Ht-29 human colon cancer cell lines. Invest New Drugs 2020; 38: 990-1002.
[PMID: 31520321]
[58]
Marwa IS, Rania MG, Mohamed AM, Hassan ME. Design, synthesis and molecular modeling of new 1,3,5-triazine derivatives as anticancer agents. Pharma Chem 2019; 11(5): 7-14.
[59]
Shuttleworth SJ, Silva FA, Cecil AR, et al. Progress in the preclinical discovery and clinical development of class I and dual class I/IV phosphoinositide 3-kinase (PI3K) inhibitors. Curr Med Chem 2011; 18(18): 2686-714.
[http://dx.doi.org/10.2174/092986711796011229] [PMID: 21649578]
[60]
Meadows SA, Vega F, Kashishian A, et al. PI3Kδ inhibitor, GS-1101 (CAL-101), attenuates pathway signaling, induces apoptosis, and overcomes signals from the microenvironment in cellular models of Hodgkin lymphoma. Blood 2012; 119(8): 1897-900.
[http://dx.doi.org/10.1182/blood-2011-10-386763] [PMID: 22210877]
[61]
Lannutti BJ, Meadows SA, Herman SEM, et al. CAL-101, a p110δ selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 2011; 117(2): 591-4.
[http://dx.doi.org/10.1182/blood-2010-03-275305] [PMID: 20959606]
[62]
Verheijen JC, Richard DJ, Curran K, Kaplan J, Yu K, Zask A. 2-Arylureidophenyl-4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)triazines as highly potent and selective ATP competitive mTOR inhibitors: Optimization of human microsomal stability. Bioorg Med Chem Lett 2010; 20(8): 2648-53.
[http://dx.doi.org/10.1016/j.bmcl.2010.02.031] [PMID: 20223663]
[63]
Ma ZY, Zhang XH, Li C, Zheng Y, Yang G. Design and synthesis of 3-substitued methylenethiochroman-4-ones-as anticancer agents. Chem Res Chin Univ 2011; 27(5): 787-91.
[64]
Bai F, Liu H, Tong L, et al. Discovery of novel selective inhibitors for EGFR-T790M/L858R. Bioorg Med Chem Lett 2012; 22(3): 1365-70.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.067] [PMID: 22227214]
[65]
Sielecki TM, Boylan JF, Benfield PA, Trainor GL. Cyclin-dependent kinase inhibitors: useful targets in cell cycle regulation. J Med Chem 2000; 43(1): 1-18.
[http://dx.doi.org/10.1021/jm990256j] [PMID: 10633033]
[66]
Maccioni RB, Otth C, Concha II, Muñoz JP. The protein kinase Cdk5. Eur J Biochem 2001; 268(6): 1518-27.
[http://dx.doi.org/10.1046/j.1432-1327.2001.02024.x] [PMID: 11248668]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy