1,3,5-Triazine Analogs: A Potent Anticancer Scaffold

Author(s): Rajeev Kumar*, Neeraj Kumar, Ram Kumar Roy, Anita Singh.

Journal Name: Current Signal Transduction Therapy

Volume 14 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: This review presents the exhaustive exploration of 1,3,5-triazine scaffold for development of analogs of anticancer drugs, over the last century. In the recent years, striazine moiety has been one of the most studied moiety, showing broad-spectrum pharmacological activities such as antibacterial, antifungal, analgesic, anti-HIV, antileishmanial, antitrypanosomal, antimalarial and antiviral. Nowadays, many boffins are have become interested in novel synthesis of s-triazine derivatives because of low cost and ease of availability.

Methods: This scaffold has been extensively investigated mainly in the past decade. Many products have been synthesized from different starting materials and these synthetic products possess anticancer potential against various cell lines.

Results: Many 1,3,5-triazine analogs exhibited significant anticancer activity in various models and cell lines exhibiting different mechanisms. Some analogs have also shown good pharmacokinetic parameters with less IC50 values.

Conclusion: Various 1,3,5-triazine analogs have shown potent activities and may be regarded as clinical candidates for future anticancer formulations. This review may be helpful to those researchers seeking required information with regard to the drug design and medicinal properties of 1,3,5-triazine derivatives for selected targets. This review may also offer help to find and improve clinically viable anticancer molecules.

Keywords: s-Triazine, anticancer, epidermal growth factor receptor, cytotoxic, vascular endothelial growth factor, chemotherapy.

[1]
Kumar R, Gupta L, Pal P, et al. Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents. Eur J Med Chem 2010; 45(6): 2265-76.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.001] [PMID: 20207053]
[2]
Ray S, Smith FR, Bridson JN, et al. Thiopyridyl triazine analogs and their platinum complexes: a new class of potential antitumor agents. Inorg Chim Acta 1994; 227(1): 175-9.
[http://dx.doi.org/10.1016/0020-1693(94)04149-0]
[3]
Chandregowda V, Kush AK, Chandrasekara Reddy G. Synthesis and in vitro antitumor activities of novel 4-anilinoquinazoline derivatives. Eur J Med Chem 2009; 44(7): 3046-55.
[http://dx.doi.org/10.1016/j.ejmech.2008.07.023] [PMID: 18771819]
[4]
Arya K, Dandia A. Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines. Bioorg Med Chem Lett 2007; 17(12): 3298-304.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.007] [PMID: 17449247]
[5]
Venkatesan AM, Dehnhardt CM, Delos Santos E, et al. Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5′-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor. J Med Chem 2010; 53(6): 2636-45.
[http://dx.doi.org/10.1021/jm901830p] [PMID: 20166697]
[6]
Lemke TL, Williams DA, Roche VF, et al. Foy’s Principles of medicinal chemistry, 6th edi. New Delhi: Wolters Kluwer Pvt Ltd 2010.
[7]
Zheng M, Xu C, Ma J, et al. Synthesis and antitumor evaluation of a novel series of triaminotriazine derivatives. Bioorg Med Chem 2007; 15(4): 1815-27.
[http://dx.doi.org/10.1016/j.bmc.2006.11.028] [PMID: 17157510]
[8]
Menicagli R, Samaritani S, Signore G, Vaglini F, Dalla Via L. In vitro cytotoxic activities of 2-alkyl-4,6-diheteroalkyl-1,3,5-triazines: new molecules in anticancer research. J Med Chem 2004; 47(19): 4649-52.
[http://dx.doi.org/10.1021/jm0495374] [PMID: 15341480]
[9]
Kar A. Medicinal Chemistry, 5th ed. New age international publishers, New Dehi 2010 In.
[10]
Stukov AN, Korsakov MV, Khrapova TN, Kil’maeva NE, Kraĭz BO. [Effect of dioxadet on tumors transplanted to the brain Vopr Onkol 1986; 32(10): 64-7.
[PMID: 3776129]
[11]
Stukov AN, Filov VA, Kon’kov SA, Ivin BA. [The pharmacological properties of preparations from the aziridinyl triazine group Eksp Klin Farmakol 1996; 59(1): 58-60.
[PMID: 8704637]
[12]
Bespalov VG, Beliaeva OA, Panchenko AV, et al. [Antitumor activity of dioxadet compared with cisplatin on ascitic ovarian tumor in rats Vopr Onkol 2011; 57(6): 771-4.
[PMID: 22416396]
[13]
Saczewski 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]
[14]
Shawver LK, Lipson KE, Brandt BM, et al. Receptor tyrosine kinases as targets for inhibition of angiogenesis. Drug Discov Today 1997; 2(2): 50-63.
[http://dx.doi.org/10.1016/S1359-6446(96)10053-2]
[15]
Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med 2003; 9(6): 669-76.
[http://dx.doi.org/10.1038/nm0603-669] [PMID: 12778165]
[16]
Yu Q. The dynamic roles of angiopoietins in tumor angiogenesis. Future Oncol 2005; 1(4): 475-84.
[http://dx.doi.org/10.2217/14796694.1.4.475] [PMID: 16556024]
[17]
Visconti RP, Richardson CD, Sato TN. Orchestration of angiogenesis and arteriovenous contribution by angiopoietins and vascular endothelial growth factor (VEGF). Proc Natl Acad Sci USA 2002; 99(12): 8219-24.
[http://dx.doi.org/10.1073/pnas.122109599] [PMID: 12048246]
[18]
Cho CH, Kammerer RA, Lee HJ, et al. COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity. Proc Natl Acad Sci USA 2004; 101(15): 5547-52.
[http://dx.doi.org/10.1073/pnas.0307574101] [PMID: 15060279]
[19]
Suri C, Jones PF, Patan S, et al. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 1996; 87(7): 1171-80.
[http://dx.doi.org/10.1016/S0092-8674(00)81813-9] [PMID: 8980224]
[20]
Scharpfenecker M, Fiedler U, Reiss Y, Augustin HG. The Tie-2 ligand angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism. J Cell Sci 2005; 118(Pt 4): 771-80.
[http://dx.doi.org/10.1242/jcs.01653] [PMID: 15687104]
[21]
Lobov IB, Brooks PC, Lang RA. Angiopoietin-2 displays VEGF-dependent modulation of capillary structure and endothelial cell survival in vivo. Proc Natl Acad Sci USA 2002; 99(17): 11205-10.
[http://dx.doi.org/10.1073/pnas.172161899] [PMID: 12163646]
[22]
Oliner J, Min H, Leal J, et al. Suppression of angiogenesis and tumor growth by selective inhibition of angiopoietin-2. Cancer Cell 2004; 6(5): 507-16.
[http://dx.doi.org/10.1016/j.ccr.2004.09.030] [PMID: 15542434]
[23]
Hodous BL, Geuns-Meyer SD, Hughes PE, et al. Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine Tie-2 kinase inhibitor. J Med Chem 2007; 50(4): 611-26.
[http://dx.doi.org/10.1021/jm061107l] [PMID: 17253678]
[24]
Reynolds LP, Grazul-Bilska AT, Redmer DA. Angiogenesis in the female reproductive organs: pathological implications. Int J Exp Pathol 2002; 83(4): 151-63.
[http://dx.doi.org/10.1046/j.1365-2613.2002.00277.x] [PMID: 12485460]
[25]
Kim KJ, Li B, Winer J, et al. Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 1993; 362(6423): 841-4.
[http://dx.doi.org/10.1038/362841a0] [PMID: 7683111]
[26]
Kabbinavar F, Hurwitz HI, Fehrenbacher L, et al. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol 2003; 21(1): 60-5.
[http://dx.doi.org/10.1200/JCO.2003.10.066] [PMID: 12506171]
[27]
Yang JC, Haworth L, Sherry RM, et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 2003; 349(5): 427-34.
[http://dx.doi.org/10.1056/NEJMoa021491] [PMID: 12890841]
[28]
Prewett M, Huber J, Li Y, et al. Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res 1999; 59(20): 5209-18.
[PMID: 10537299]
[29]
Baindur N, Chadha N, Brandt BM, et al. 2-Hydroxy-4,6-diamino-[1,3,5]triazines: a novel class of VEGF-R2 (KDR) tyrosine kinase inhibitors. J Med Chem 2005; 48(6): 1717-20.
[http://dx.doi.org/10.1021/jm049372z] [PMID: 15771417]
[30]
Shen TL, Park AY, Alcaraz A, et al. Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis. J Cell Biol 2005; 169(6): 941-52.
[http://dx.doi.org/10.1083/jcb.200411155] [PMID: 15967814]
[31]
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]
[32]
Prien O. The gatekeeper: friend or foe in identifying the next generation of kinase inhibitors. ChemMedChem 2006; 1(11): 1195-6.
[http://dx.doi.org/10.1002/cmdc.200600163] [PMID: 17009360]
[33]
Ban HS, Onagi S, Uno M, Nabeyama W, Nakamura H. Allene as an alternative functional group for drug design: effect of C--C multiple bonds conjugated with quinazolines on the inhibition of EGFR tyrosine kinase. ChemMedChem 2008; 3(7): 1094-103.
[http://dx.doi.org/10.1002/cmdc.200800073] [PMID: 18465761]
[34]
Saijo N. Targeted therapies: Tyrosine-kinase inhibitors--new standard for NSCLC therapy. Nat Rev Clin Oncol 2010; 7(11): 618-9.
[http://dx.doi.org/10.1038/nrclinonc.2010.168] [PMID: 20981125]
[35]
Janku F, Stewart DJ, Kurzrock R. Targeted therapy in non-small-cell lung cancer--is it becoming a reality? Nat Rev Clin Oncol 2010; 7(7): 401-14.
[http://dx.doi.org/10.1038/nrclinonc.2010.64] [PMID: 20551945]
[36]
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]
[37]
Yaguchi S, Fukui Y, Koshimizu I, et al. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J Natl Cancer Inst 2006; 98(8): 545-56.
[http://dx.doi.org/10.1093/jnci/djj133] [PMID: 16622124]
[38]
Poulsen A, Williams M, Nagaraj HM, et al. Structure-based optimization of morpholino-triazines as PI3K and mTOR inhibitors. Bioorg Med Chem Lett 2012; 22(2): 1009-13.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.001] [PMID: 22197143]
[39]
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]
[40]
Kim YJ, Sackett DL, Schapira M, et al. Identification of 12Cysbeta on tubulin as the binding site of tubulyzine. Bioorg Med Chem 2006; 14(4): 1169-75.
[http://dx.doi.org/10.1016/j.bmc.2005.09.069] [PMID: 16266809]
[41]
Popowycz F, Schneider C, Debonis S, et al. Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives. Bioorg Med Chem 2009; 17(9): 3471-8.
[http://dx.doi.org/10.1016/j.bmc.2009.03.007] [PMID: 19349183]
[42]
Nie Z, Perretta C, Erickson P, et al. Structure-based design and synthesis of novel macrocyclic pyrazolo[1,5-a] [1,3,5]triazine compounds as potent inhibitors of protein kinase CK2 and their anticancer activities. Bioorg Med Chem Lett 2008; 18(2): 619-23.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.074] [PMID: 18055206]
[43]
Suda A, Koyano H, Hayase T, et al. Design and synthesis of novel macrocyclic 2-amino-6-arylpyrimidine Hsp90 inhibitors. Bioorg Med Chem Lett 2012; 22(2): 1136-41.
[http://dx.doi.org/10.1016/j.bmcl.2011.11.100] [PMID: 22192591]
[44]
Brough PA, Barril X, Borgognoni J, et al. Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem 2009; 52(15): 4794-809.
[http://dx.doi.org/10.1021/jm900357y] [PMID: 19610616]
[45]
Lee T, Seo YH. Targeting the hydrophobic region of Hsp90's ATP binding pocket with novel 1,3,5-triazines. Bioorg Med Chem Lett 2013; 23(23): 6427-31.
[http://dx.doi.org/10.1016/j.bmcl.2013.09.050] [PMID: 24125885]
[46]
Kuo GH, Deangelis A, Emanuel S, et al. Synthesis and identification of [1,3,5]triazine-pyridine biheteroaryl as a novel series of potent cyclin-dependent kinase inhibitors. J Med Chem 2005; 48(14): 4535-46.
[http://dx.doi.org/10.1021/jm040214h] [PMID: 15999992]
[47]
Popowycz F, Fournet G, Schneider C, et al. Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue. J Med Chem 2009; 52(3): 655-63.
[http://dx.doi.org/10.1021/jm801340z] [PMID: 19128055]
[48]
Ma X, Chui WK. Antifolate and antiproliferative activity of 6,8,10-triazaspiro[4.5]deca-6,8-dienes and 1,3,5-triazaspiro[5.5]undeca-1,3-dienes. Bioorg Med Chem 2010; 18(2): 737-43.
[http://dx.doi.org/10.1016/j.bmc.2009.11.065] [PMID: 20036565]
[49]
Ma X, Woon RSS, Ho PCL, Chui WK. Antiproliferative activity against MCF-7 breast cancer cells by diamino-triazaspirodiene antifolates. Chem Biol Drug Des 2009; 74(3): 322-6.
[http://dx.doi.org/10.1111/j.1747-0285.2009.00860.x] [PMID: 19703036]
[50]
Ma X, Xiang G, Yap CW, Chui WK. 3D-QSAR Study on dihydro-1,3,5-triazines and their spiro derivatives as DHFR inhibitors by comparative molecular field analysis (CoMFA). Bioorg Med Chem Lett 2012; 22(9): 3194-7.
[http://dx.doi.org/10.1016/j.bmcl.2012.03.041] [PMID: 22483391]
[51]
Dolzhenko AV, Tan BJ, Dolzhenko AV, et al. 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 Fluor Chem 2008; 129(5): 429-34.
[http://dx.doi.org/10.1016/j.jfluchem.2008.02.007]
[52]
Corbett TH, Leopold WR, Dykes DJ, Roberts BJ, Griswold DP Jr, Schabel FM Jr. Toxicity and anticancer activity of a new triazine antifolate (NSC 127755). Cancer Res 1982; 42(5): 1707-15.
[PMID: 7066891]
[53]
Bag S, Tawari NR, Degani MS, Queener SF. Design, synthesis, biological evaluation and computational investigation of novel inhibitors of dihydrofolate reductase of opportunistic pathogens. Bioorg Med Chem 2010; 18(9): 3187-97.
[http://dx.doi.org/10.1016/j.bmc.2010.03.031] [PMID: 20363634]
[54]
Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer 2001; 1(3): 194-202.
[http://dx.doi.org/10.1038/35106079] [PMID: 11902574]
[55]
Jenuwein T, Allis CD. Translating the histone code. Science 2001; 293(5532): 1074-80.
[http://dx.doi.org/10.1126/science.1063127] [PMID: 11498575]
[56]
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006; 6(1): 38-51.
[http://dx.doi.org/10.1038/nrc1779] [PMID: 16397526]
[57]
Paquin I, Raeppel S, Leit S, et al. Design and synthesis of 4-[(s-triazin-2-ylamino)methyl]-N-(2-aminophenyl)-benzamides and their analogues as a novel class of histone deacetylase inhibitors. Bioorg Med Chem Lett 2008; 18(3): 1067-71.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.009] [PMID: 18160287]
[58]
Supuran CT, Scozzafava A, Casini A. Carbonic anhydrase inhibitors. Med Res Rev 2003; 23(2): 146-89.
[http://dx.doi.org/10.1002/med.10025] [PMID: 12500287]
[59]
Alterio V, Di Fiore A, D’Ambrosio K, Supuran CT, De Simone G. Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem Rev 2012; 112(8): 4421-68.
[http://dx.doi.org/10.1021/cr200176r] [PMID: 22607219]
[60]
Supuran CT. Structure-based drug discovery of carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem 2012; 27(6): 759-72.
[http://dx.doi.org/10.3109/14756366.2012.672983] [PMID: 22468747]
[61]
Saluja AK, Tiwari M, Vullo D, Supuran CT. Substituted benzene sulfonamides incorporating 1,3,5-triazinyl moieties potently inhibit human carbonic anhydrases II, IX and XII. Bioorg Med Chem Lett 2014; 24(5): 1310-4.
[http://dx.doi.org/10.1016/j.bmcl.2014.01.048] [PMID: 24507918]
[62]
Carta F, Garaj V, Maresca A, et al. Sulfonamides incorporating 1,3,5-triazine moieties selectively and potently inhibit carbonic anhydrase transmembrane isoforms IX, XII and XIV over cytosolic isoforms I and II: Solution and X-ray crystallographic studies. Bioorg Med Chem 2011; 19(10): 3105-19.
[http://dx.doi.org/10.1016/j.bmc.2011.04.005] [PMID: 21515057]
[63]
Shekhar MPV, Lyakhovich A, Visscher DW, Heng H, Kondrat N. Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation. Cancer Res 2002; 62(7): 2115-24.
[PMID: 11929833]
[64]
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]
[65]
Ryu BJ, Kim S, Min B, et al. Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor. Cancer Lett 2014; 349(1): 45-50.
[http://dx.doi.org/10.1016/j.canlet.2014.03.024] [PMID: 24704155]
[66]
Al-Khamees HA. Synthesis of new derivatives of 1,3,5-hexahydro-s-triazine as potential anticancer agents. Arch Pharm Res 1990; 13(1): 19-23.
[http://dx.doi.org/10.1007/BF02857828]
[67]
Hranjec M, Pavlovic G, Karminski-Zamola G. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2-a]benzimidazoles. J Mol Struct 2012; 1007: 242-51.
[http://dx.doi.org/10.1016/j.molstruc.2011.10.054]
[68]
Brzozowski Z, Saczewski F. Synthesis and antitumor activity of novel 2-amino-4-(3,5,5-trimethyl-2-pyrazolino)-1,3,5-triazine derivatives. Eur J Med Chem 2002; 37(9): 709-20.
[http://dx.doi.org/10.1016/S0223-5234(02)01379-X] [PMID: 12350288]
[69]
Kotha S, Kashinath D, Lopus M, et al. Synthesis of nano-sized C3-symmetric 2,4,6-triphenyl-1,3,5-s-triazine and 1,3,5-triphenyl benzene analogs via the trimerization followed by Suzuki-miyaura cross coupling or O-alkylation reactions and their biological evaluation. Indian J Chem 2009; 48B: 1766-70.
[70]
Rubino S, Portanova P, Girasolo A, Calvaruso G, Orecchio S, Stocco GC. Synthetic, structural and biochemical studies of polynuclear platinum(II) complexes with heterocyclic ligands. Eur J Med Chem 2009; 44(3): 1041-8.
[http://dx.doi.org/10.1016/j.ejmech.2008.06.023] [PMID: 18676063]
[71]
Pruchnik FP, Jakimowicz P, Ciunik Z, et al. Rhodium(III) complexes with polypyridyls and pyrazole and their antitumor activity. Inorg Chim Acta 2002; 334: 59-66.
[http://dx.doi.org/10.1016/S0020-1693(02)00776-4]
[72]
Lakomska I, Golankiewicz B, Wietrzyk J, et al. Synthesis, spectroscopical characterization and the biological activity in vitro of new platinum(II) complexes with imidazo[1,5-a]-1,3,5-triazine derivatives and dimethylsulfoxide. Inorg Chim Acta 2005; 358(6): 1911-7.
[http://dx.doi.org/10.1016/j.ica.2004.12.033]
[73]
De Domenico I, McVey Ward D, Kaplan J. Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol 2008; 9(1): 72-81.
[http://dx.doi.org/10.1038/nrm2295] [PMID: 17987043]
[74]
Richardson DR, Baker E. The uptake of iron and transferrin by the human malignant melanoma cell. Biochim Biophys Acta 1990; 1053(1): 1-12.
[http://dx.doi.org/10.1016/0167-4889(90)90018-9] [PMID: 2364114]
[75]
Hileti D, Panayiotidis P, Hoffbrand AV. Iron chelators induce apoptosis in proliferating cells. Br J Haematol 1995; 89(1): 181-7.
[http://dx.doi.org/10.1111/j.1365-2141.1995.tb08927.x] [PMID: 7833261]
[76]
Sun D, Melman G, Letourneau NJ, Hays AM, Melman A. Synthesis and antiproliferating activity of iron chelators of hydroxyamino-1,3,5-triazine family. Bioorg Med Chem Lett 2010; 20(2): 458-60.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.130] [PMID: 20005708]
[77]
Beisler JA, Abbasi MM, Kelley JA, Driscoll JS. Synthesis and antitumor activity of dihydro-5-azacytidine, a hydrolytically stable analogue of 5-azacytidine. J Med Chem 1977; 20(6): 806-12.
[http://dx.doi.org/10.1021/jm00216a013] [PMID: 69026]
[78]
Gaubert G, Mathé C, Imbach J, et al. Unnatural enantiomers of 5-azacytidine analogues: syntheses and enzymatic properties. Eur J Med Chem 2000; 35(11): 1011-9.
[http://dx.doi.org/10.1016/S0223-5234(00)01184-3] [PMID: 11137229]
[79]
Nguyen AN, Hollenbach PW, Richard N, et al. Azacitidine and decitabine have different mechanisms of action in non-small cell lung cancer cell lines. Lung Cancer (Auckl) 2010; 1: 119-40.
[http://dx.doi.org/10.2147/LCTT.S11726] [PMID: 28210112]
[80]
Saripinar E, Geçen N, Sahin K, Yanmaz E. Pharmacophore identification and bioactivity prediction for triaminotriazine derivatives by electron conformational-genetic algorithm QSAR method. Eur J Med Chem 2010; 45(9): 4157-68.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.007] [PMID: 20598401]
[81]
Wittine K, Babić MS, Košutić M, et al. The new 5- or 6-azapyrimidine and cyanuric acid derivatives of l-ascorbic acid bearing the free C-5 hydroxy or C-4 amino group at the ethylenic spacer: CD-spectral absolute configuration determination and biological activity evaluations. Eur J Med Chem 2011; 46(7): 2770-85.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.066] [PMID: 21524828]
[82]
Saczewski 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]
[83]
Machakanur SS, Patil BR, Badiger DS, et al. Synthesis, characterization and anticancer evaluation of novel tri-arm star shaped 1,3,5-triazine hydrazones. J Mol Struct 2012; 1011: 121-7.
[http://dx.doi.org/10.1016/j.molstruc.2011.12.023]
[84]
Brzozowski Z, Saczewski F, Gdaniec M. Synthesis, structural characterization and antitumor activity of novel 2,4-diamino-1,3,5-triazine derivatives. Eur J Med Chem 2000; 35(12): 1053-64.
[http://dx.doi.org/10.1016/S0223-5234(00)01194-6] [PMID: 11248404]
[85]
Pomarnacka E, Bednarski P, Grunert R, Reszka P. Synthesis and anticancer activity of novel 2-amino-4-(4-phenylpiperazino)- 1,3,5-triazine derivatives. Acta Pol Pharm 2004; 61(6): 461-6.
[PMID: 15794339]
[86]
Patel RV, Kumari P, Rajani DP, Chikhalia KH. Synthesis and studies of novel 2-(4-cyano-3-trifluoromethylphenyl amino)-4-(quinoline-4-yloxy)-6-(piperazinyl/piperidinyl)-s-triazines as potential antimicrobial, antimycobacterial and anticancer agents. Eur J Med Chem 2011; 46(9): 4354-65.
[http://dx.doi.org/10.1016/j.ejmech.2011.07.006] [PMID: 21794959]
[87]
Balaha MF, El-Hamamsy MH, El-Din NAS, et al. 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]
[88]
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]
[89]
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]
[90]
El-Faham A, Soliman SM, Ghabbour HA, et al. Ultrasonic promoted synthesis of novel s-triazine-Schiff base derivatives; molecular structure, spectroscopic studies and their preliminary anti-proliferative activities. J Mol Struct 2016; 1125: 121-35.
[http://dx.doi.org/10.1016/j.molstruc.2016.06.061]
[91]
Vallejo M, Castro MA, Medarde M, et al. Novel bile acid derivatives (BANBs) with cytostatic activity obtained by conjugation of their side chain with nitrogenated bases. Biochem Pharmacol 2007; 73(9): 1394-404.
[http://dx.doi.org/10.1016/j.bcp.2006.12.027] [PMID: 17257589]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 14
ISSUE: 2
Year: 2019
Page: [87 - 106]
Pages: 20
DOI: 10.2174/1574362413666180221113805
Price: $58

Article Metrics

PDF: 25
HTML: 4

Special-new-year-discount