1,3,5-Triazine-azole Hybrids and their Anticancer Activity

Author(s): Hua Guo*, Quan-Ping Diao

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 16 , 2020


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Graphical Abstract:


Abstract:

1,3,5-Triazine and azole can interact with various therapeutic targets, and their derivatives possess promising in vitro and in vivo anticancer activity. Hybrid molecules have the potential to enhance efficiency, overcome drug resistance and reduce side effects, and many hybrid molecules are under different phases of clinical trials, so hybridization of 1,3,5-triazine with azole may provide valuable therapeutic intervention for the treatment of cancer. Substantial efforts have been made to develop azole-containing 1,3,5-triazine hybrids as novel anticancer agents, and some of them exhibited excellent activity. This review emphasizes azole-containing 1,3,5-triazine hybrids with potential anticancer activity, and the structure-activity relationships as well as the mechanisms of action are also discussed to provide comprehensive and target-oriented information for the development of this kind of anticancer drugs.

Keywords: 1, 3, 5-triazine, Azole, Hybrid molecules, Anticancer, Structure-activity relationship, In vitro.

[1]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2018. CA Cancer J. Clin., 2018, 68(1), 7-30.
[http://dx.doi.org/10.3322/caac.21442] [PMID: 29313949]
[3]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[4]
World Health Organization. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. Available from:. https://www.who.int/cancer/PRGlobocanFinal.pdf (Accessed 2018).
[5]
Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. Int. Agency Res. Can., Available from:. https://www.iarc.fr/featured-news/latest-global-cancer-data-cancer-burden-rises-to-18-1-million-new-cases-and-9-6-million-cancer-deaths-in-2018/ (Accessed 2018).
[6]
Cancer Tomorrow, Estimated number of incident cases from 2018 to 2040, all cancers, both sexes, all age. Available from:. https://gco.iarc.fr/tomorrow/graphic-isotype?type=0&population=900&mode=population&sex=0&cancer=39&age_group=value&apc_male=0&apc_female=0.
[7]
Siegel, R.L.; Jemal, A.; Wender, R.C.; Gansler, T.; Ma, J.; Brawley, O.W. An assessment of progress in cancer control. CA Cancer J. Clin., 2018, 68(5), 329-339.
[http://dx.doi.org/10.3322/caac.21460] [PMID: 30191964]
[8]
Gao, F.; Zhang, X.; Wang, T.; Xiao, J. Quinolone hybrids and their anti-cancer activities: An overview. Eur. J. Med. Chem., 2019, 165, 59-79.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.017] [PMID: 30660827]
[9]
Chatterjee, N.; Bivona, T.G. Polytherapy and targeted cancer drug resistance. Trends Cancer, 2019, 5(3), 170-182.
[http://dx.doi.org/10.1016/j.trecan.2019.02.003] [PMID: 30898264]
[10]
Aleksakhina, S.N.; Kashyap, A.; Imyanitov, E.N. Mechanisms of acquired tumor drug resistance. BBA-Rev. Cancer, 2019, 1872, e188310
[11]
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]
[12]
Lim, F.P.L.; Dolzhenko, A.V. 1,3,5-Triazine-based analogues of purine: from isosteres to privileged scaffolds in medicinal chemistry. Eur. J. Med. Chem., 2014, 85, 371-390.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.112] [PMID: 25105925]
[13]
Liu, H.; Long, S.; Rakesh, K.P.; Zha, G.F. Structure-activity relationships (SAR) of triazine derivatives: Promising antimicrobial agents. Eur. J. Med. Chem., 2020, 185, 111804
[http://dx.doi.org/10.1016/j.ejmech.2019.111804] [PMID: 31675510]
[14]
Haiba, N.S.; Khalil, H.H.; Moniem, M.A.; El-Wakil, M.H.; Bekhit, A.A.; Khattab, S.N. Design, synthesis and molecular modeling studies of new series of s-triazine derivatives as antimicrobial agents against multi-drug resistant clinical isolates. Bioorg. Chem., 2019, 89, 103013
[http://dx.doi.org/10.1016/j.bioorg.2019.103013] [PMID: 31174040]
[15]
Hunt, J.C.A.; Briggs, E.; Clarke, E.D.; Whittingham, W.G. Synthesis and SAR studies of novel antifungal 1,2,3-triazines. Bioorg. Med. Chem. Lett., 2007, 17(18), 5222-5226.
[http://dx.doi.org/10.1016/j.bmcl.2007.06.076] [PMID: 17656087]
[16]
Li, L.X.; Jiao, J.; Wang, X.B.; Chen, M.; Fu, X.C.; Si, W.J.; Yang, C.L. Synthesis, characterization, and antifungal activity of novel benzo[4,5]imidazo[1,2-d][1,2,4]triazine derivatives. Molecules, 2018, 23(4) e746
[http://dx.doi.org/10.3390/molecules23040746] [PMID: 29570685]
[17]
Marín-Ocampo, L.; Veloza, L.A.; Abonia, R.; Sepúlveda-Arias, J.C. Anti-inflammatory activity of triazine derivatives: A systematic review. Eur. J. Med. Chem., 2019, 162, 435-447.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.027] [PMID: 30469039]
[18]
Shinde, R.S.; Salunke, S.D. Synthesis and studies of novel piperidine-substituted triazine derivatives as potential anti-inflammatory and antimicrobial agents. J. Chem. Pharm. Res., 2015, 7(7), 704-714.
[19]
Chauhan, K.; Sharma, M.; Shivahare, R.; Debnath, U.; Gupta, S.; Prabhakar, Y.S.; Chauhan, P.M.S. Discovery of triazine mimetics as potent antileishmanial agents. ACS Med. Chem. Lett., 2013, 4(11), 1108-1113.
[http://dx.doi.org/10.1021/ml400317e] [PMID: 24900613]
[20]
Baréa, P.; Barbosa, V.A.; Bidóia, D.L.; de Paula, J.C.; Stefanello, T.F.; da Costa, W.F.; Nakamura, C.V.; Sarragiotto, M.H. Synthesis, antileishmanial activity and mechanism of action studies of novel β-carboline-1,3,5-triazine hybrids. Eur. J. Med. Chem., 2018, 150, 579-590.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.014] [PMID: 29549842]
[21]
Patel, R.V.; Keum, Y.S.; Park, S.W. 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), 768-789.
[http://dx.doi.org/10.2174/1389557514666140622205904] [PMID: 24958216]
[22]
Manohar, S.; Khan, S.I.; Rawat, D.S. Synthesis of 4-aminoquinoline-1,2,3-triazole and 4-aminoquinoline-1,2,3-triazole-1,3,5-triazine hybrids as potential antimalarial agents. Chem. Biol. Drug Des., 2011, 78(1), 124-136.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01115.x] [PMID: 21457474]
[23]
Patel, A.B.; Patel, R.V.; Kumari, P.; Rajani, D.P.; Chikhalia, K.H. Synthesis of potential antitubercular and antimicrobial s-triazine-based scaffolds via Suzuki cross-coupling reaction. Med. Chem. Res., 2013, 22, 367-381.
[http://dx.doi.org/10.1007/s00044-012-0041-y]
[24]
Sunduru, N.; Gupta, L.; Chaturvedi, V.; Dwivedi, R.; Sinha, S.; Chauhan, P.M.S. Discovery of new 1,3,5-triazine scaffolds with potent activity against Mycobacterium tuberculosis H37Rv. Eur. J. Med. Chem., 2010, 45(8), 3335-3345.
[http://dx.doi.org/10.1016/j.ejmech.2010.04.017] [PMID: 20452706]
[25]
Tang, X.; Su, S.; Chen, M.; He, J.; Xia, R.; Guo, T.; Chen, Y.; Zhang, C.; Wang, J.; Xue, W. Novel chalcone derivatives containing a 1,2,4-triazine moiety: Design, synthesis, antibacterial and antiviral activities. RSC Advances, 2019, 9(11), 6011-6020.
[http://dx.doi.org/10.1039/C9RA00618D]
[26]
Kumar, R.; Singh, A.D.; Singh, J.; Singh, H.; Roy, R.K.; Chaudhary, A. 1,2,3-Triazine scaffold as a potent biologically active moiety: a mini review. Mini Rev. Med. Chem., 2014, 14(1), 72-83.
[http://dx.doi.org/10.2174/1389557513666140103111017] [PMID: 24387709]
[27]
Kumar, R.; Kumar, N.; Roy, R.K.; Singh, A. 1,3,5-Triazine analogs: A potent anticancer scaffold. Curr. Signal Transduct. Ther., 2019, 14(2), 87-106.
[http://dx.doi.org/10.2174/1574362413666180221113805]
[28]
Cascioferro, S.; Parrino, B.; Spanò, V.; Carbone, A.; Montalbano, A.; Barraja, P.; Diana, P.; Cirrincione, G. 1,3,5-Triazines: A promising scaffold for anticancer drugs development. Eur. J. Med. Chem., 2017, 142, 523-549.
[http://dx.doi.org/10.1016/j.ejmech.2017.09.035] [PMID: 29046238]
[29]
Gao, F.; Wang, T.; Xiao, J.; Huang, G. Antibacterial activity study of 1,2,4-triazole derivatives. Eur. J. Med. Chem., 2019, 173, 274-281.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.043] [PMID: 31009913]
[30]
Bozorov, K.; Zhao, J.; Aisa, H.A. 1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview. Bioorg. Med. Chem., 2019, 27(16), 3511-3531.
[http://dx.doi.org/10.1016/j.bmc.2019.07.005] [PMID: 31300317]
[31]
Gao, C.; Chang, L.; Xu, Z.; Yan, X.F.; Ding, C.; Zhao, F.; Wu, X.; Feng, L.S. Recent advances of tetrazole derivatives as potential anti-tubercular and anti-malarial agents. Eur. J. Med. Chem., 2019, 163, 404-412.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.001] [PMID: 30530192]
[32]
Xu, Z.; Gao, C.; Ren, Q.C.; Song, X.F.; Feng, L.S.; Lv, Z.S. Recent advances of pyrazole-containing derivatives as anti-tubercular agents. Eur. J. Med. Chem., 2017, 139, 429-440.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.059] [PMID: 28818767]
[33]
Zhang, S.; Xu, Z.; Gao, C.; Ren, Q.C.; Chang, L.; Lv, Z.S.; Feng, L.S. Triazole derivatives and their anti-tubercular activity. Eur. J. Med. Chem., 2017, 138, 501-513.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.051] [PMID: 28692915]
[34]
Xu, Z.; Zhao, S.J.; Liu, Y. 1,2,3-Triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms and structure-activity relationships. Eur. J. Med. Chem., 2019, 183, 111700
[http://dx.doi.org/10.1016/j.ejmech.2019.111700] [PMID: 31546197]
[35]
Sharma, P.C.; Bansal, K.K.; Sharma, A.; Sharma, D.; Deep, A. Thiazole-containing compounds as therapeutic targets for cancer therapy. Eur. J. Med. Chem., 2020, 188, 112016
[http://dx.doi.org/10.1016/j.ejmech.2019.112016] [PMID: 31926469]
[36]
Hou, Y.; Shang, C.; Wang, H.; Yun, J. Isatin-azole hybrids and their anticancer activities. Arch. Pharm. (Weinheim), 2020, 353(1) e1900272
[http://dx.doi.org/10.1002/ardp.201900272] [PMID: 31691360]
[37]
Zhang, J.; Wang, S.; Ba, Y.; Xu, Z. Tetrazole hybrids with potential anticancer activity. Eur. J. Med. Chem., 2019, 178, 341-351.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.071] [PMID: 31200236]
[38]
Bennani, F.E.; Doudach, L.; Cherrah, Y.; Ramli, Y.; Karrouchi, K.; Ansar, M.; Faouzi, M.E.A. Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line. Bioorg. Chem., 2019, 97, 103470
[http://dx.doi.org/10.1016/j.bioorg.2019.103470] [PMID: 32120072]
[39]
Rewcastle, G.W.; Kolekar, S.; Buchanan, C.M.; Gamage, S.A.; Giddens, A.C.; Tsang, K.Y.; Kendall, J.D.; Singh, R.; Lee, W.J.; Smith, G.C.; Han, W.; Matthews, D.J.; Denny, W.A.; Shepherd, P.R.; Jamieson, S.M.F. Biological characterization of SN32976, a selective inhibitor of PI3K and mTOR with preferential activity to PI3Kα, in comparison to established pan PI3K inhibitors. Oncotarget, 2017, 8(29), 47725-47740.
[http://dx.doi.org/10.18632/oncotarget.17730] [PMID: 28537878]
[40]
Hao, C.; Huang, W.; Li, X.; Guo, J.; Chen, M.; Yan, Z.; Wang, K.; Jiang, X.; Song, S.; Wang, J.; Zhao, D.; Li, F.; Cheng, M. Development of 2, 4-diaminoquinazoline derivatives as potent PAK4 inhibitors by the core refinement strategy. Eur. J. Med. Chem., 2017, 131, 1-13.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.063] [PMID: 28284095]
[41]
Zhang, N.; Yu, Z.; Yang, X.; Zhou, Y.; Wang, J.; Zhang, S.L.; Wang, M.W.; He, Y. Synthesis, biological evaluation and structure-activity relationship of a novel class of PI3Kα H1047R mutant inhibitors. Eur. J. Med. Chem., 2018, 158, 707-719.
[http://dx.doi.org/10.1016/j.ejmech.2018.09.002] [PMID: 30245395]
[42]
Kong, D.; Yamori, T.; Yamazaki, K.; Dan, S. In vitro multifaceted activities of a specific group of novel phosphatidylinositol 3-kinase inhibitors on hotspot mutant PIK3CA. Invest. New Drugs, 2014, 32(6), 1134-1143.
[http://dx.doi.org/10.1007/s10637-014-0152-z] [PMID: 25152245]
[43]
Singh, A.; Thatikonda, T.; Kumar, A.; Wazir, P.; v, V.; Nandi, U.; Singh, P.P.; Singh, S.; Gupta, A.P.; Tikoo, M.K.; Singh, G.; Vishwakarma, R. Determination of ZSTK474, a novel Pan PI3K inhibitor in mouse plasma by LC-MS/MS and its application to Pharmacokinetics. J. Pharm. Biomed. Anal., 2018, 149, 387-393.
[http://dx.doi.org/10.1016/j.jpba.2017.11.031] [PMID: 29175554]
[44]
Wang, Y.; Liu, J.; Qiu, Y.; Jin, M.; Chen, X.; Fan, G.; Wang, R.; Kong, D. ZSTK474, a specific class I phosphatidylinositol 3-kinase inhibitor, induces G1 arrest and autophagy in human breast cancer MCF-7 cells. Oncotarget, 2016, 7(15), 19897-19909.
[http://dx.doi.org/10.18632/oncotarget.7658] [PMID: 26918351]
[45]
Zhao, W.; Qiu, Y.; Kong, D. Class I phosphatidylinositol 3-kinase inhibitors for cancer therapy. Acta Pharm. Sin. B, 2017, 7(1), 27-37.
[http://dx.doi.org/10.1016/j.apsb.2016.07.006] [PMID: 28119806]
[46]
Shalmali, N.; Ali, M.R.; Bawa, S. Imidazole: An essential edifice for the identification of new lead compounds and drug development. Mini Rev. Med. Chem., 2018, 18(2), 142-163.
[http://dx.doi.org/10.2174/1389557517666170228113656] [PMID: 28245779]
[47]
Yadav, S.; Narasimhan, B.; Kaur, H. Perspectives of benzimidazole derivatives as anticancer agents in the new era. Anticancer. Agents Med. Chem., 2016, 16(11), 1403-1425.
[http://dx.doi.org/10.2174/1871520616666151103113412] [PMID: 26526461]
[48]
Cortes, J.; Faderl, S.; Estey, E.; Kurzrock, R.; Thomas, D.; Beran, M.; Garcia-Manero, G.; Ferrajoli, A.; Giles, F.; Koller, C.; O’Brien, S.; Wright, J.; Bai, S.A.; Kantarjian, H. Phase I study of BMS-214662, a farnesyl transferase inhibitor in patients with acute leukemias and high-risk myelodysplastic syndromes. J. Clin. Oncol., 2005, 23(12), 2805-2812.
[http://dx.doi.org/10.1200/JCO.2005.09.005] [PMID: 15728224]
[49]
Papadimitrakopoulou, V.; Agelaki, S.; Tran, H.T.; Kies, M.; Gagel, R.; Zinner, R.; Kim, E.; Ayers, G.; Wright, J.; Khuri, F. Phase I study of the farnesyltransferase inhibitor BMS-214662 given weekly in patients with solid tumors. Clin. Cancer Res., 2005, 11(11), 4151-4159.
[http://dx.doi.org/10.1158/1078-0432.CCR-04-1659] [PMID: 15930351]
[50]
Narayanankutty, A. PI3K/AKT/mTOR pathway as a therapeutic target for colorectal cancer: A review of preclinical and clinical evidence. Curr. Drug Targets, 2019, 20(12), 1217-1226.
[http://dx.doi.org/10.2174/1389450120666190618123846] [PMID: 31215384]
[51]
Marquard, F.E.; Jücker, M. PI3K/AKT/mTOR signaling as a molecular target in head and neck cancer. Biochem. Pharmacol., 2020, 172, 113729
[http://dx.doi.org/10.1016/j.bcp.2019.113729] [PMID: 31785230]
[52]
Miller, M.S.; Pinson, J.A.; Zheng, Z.; Jennings, I.G.; Thompson, P.E. Regioselective synthesis of 5- and 6-methoxybenzimidazole-1,3,5-triazines as inhibitors of phosphoinositide 3-kinase. Bioorg. Med. Chem. Lett., 2013, 23(3), 802-805.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.076] [PMID: 23265896]
[53]
Isoyama, S.; Kajiwara, G.; Tamaki, N.; Okamura, M.; Yoshimi, H.; Nakamura, N.; Kawamura, K.; Nishimura, Y.; Namatame, N.; Yamori, T.; Dan, S. Basal expression of insulin-like growth factor 1 receptor determines intrinsic resistance of cancer cells to a phosphatidylinositol 3-kinase inhibitor ZSTK474. Cancer Sci., 2015, 106(2), 171-178.
[http://dx.doi.org/10.1111/cas.12582] [PMID: 25483727]
[54]
Lin, L.; Gaut, D.; Hu, K.; Yan, H.; Yin, D.; Koeffler, H.P. Dual targeting of glioblastoma multiforme with a proteasome inhibitor (Velcade) and a phosphatidylinositol 3-kinase inhibitor (ZSTK474). Int. J. Oncol., 2014, 44(2), 557-562.
[http://dx.doi.org/10.3892/ijo.2013.2205] [PMID: 24297065]
[55]
Barollo, S.; Bertazza, L.; Baldini, E.; Ulisse, S.; Cavedon, E.; Boscaro, M.; Pezzani, R.; Mian, C. The combination of RAF265, SB590885, ZSTK474 on thyroid cancer cell lines deeply impact on proliferation and MAPK and PI3K/Akt signaling pathways. Invest. New Drugs, 2014, 32(4), 626-635.
[http://dx.doi.org/10.1007/s10637-014-0108-3] [PMID: 24821574]
[56]
Van Dort, M.E.; Galbán, S.; Wang, H.; Sebolt-Leopold, J.; Whitehead, C.; Hong, H.; Rehemtulla, A.; Ross, B.D. Dual inhibition of allosteric mitogen-activated protein kinase (MEK) and phosphatidylinositol 3-kinase (PI3K) oncogenic targets with a bifunctional inhibitor. Bioorg. Med. Chem., 2015, 23(7), 1386-1394.
[http://dx.doi.org/10.1016/j.bmc.2015.02.053] [PMID: 25766633]
[57]
Yaguchi, S.; Fukui, Y.; Koshimizu, I.; Yoshimi, H.; Matsuno, T.; Gouda, H.; Hirono, S.; Yamazaki, K.; Yamori, T. Antitumor activity of ZSTK474, a new phosphatidylinositol 3-kinase inhibitor. J. Natl. Cancer Inst., 2006, 98(8), 545-556.
[http://dx.doi.org/10.1093/jnci/djj133] [PMID: 16622124]
[58]
Dan, S.; Yoshimi, H.; Okamura, M.; Mukai, Y.; Yamori, T. Inhibition of PI3K by ZSTK474 suppressed tumor growth not via apoptosis but G0/G1 arrest. Biochem. Biophys. Res. Commun., 2009, 379(1), 104-109.
[http://dx.doi.org/10.1016/j.bbrc.2008.12.015] [PMID: 19094964]
[59]
Zhou, Q.; Chen, Y.; Chen, X.; Zhao, W.; Zhong, Y.; Wang, R.; Jin, M.; Qiu, Y.; Kong, D. In vitro antileukemia activity of ZSTK474 on K562 and multidrug resistant K562/A02 cells. Int. J. Biol. Sci., 2016, 12(6), 631-638.
[http://dx.doi.org/10.7150/ijbs.14878] [PMID: 27194941]
[60]
Zhao, W.; Guo, W.; Zhou, Q.; Ma, S.N.; Wang, R.; Qiu, Y.; Jin, M.; Duan, H.Q.; Kong, D. In vitro antimetastatic effect of phosphatidylinositol 3-kinase inhibitor ZSTK474 on prostate cancer PC3 cells. Int. J. Mol. Sci., 2013, 14(7), 13577-13591.
[http://dx.doi.org/10.3390/ijms140713577] [PMID: 23812078]
[61]
Namatame, N.; Tamaki, N.; Yoshizawa, Y.; Okamura, M.; Nishimura, Y.; Yamazaki, K.; Tanaka, M.; Nakamura, T.; Semba, K.; Yamori, T.; Yaguchi, S.I.; Dan, S. Antitumor profile of the PI3K inhibitor ZSTK474 in human sarcoma cell lines. Oncotarget, 2018, 9(80), 35141-35161.
[http://dx.doi.org/10.18632/oncotarget.26216] [PMID: 30416685]
[62]
Kong, D.; Okamura, M.; Yoshimi, H.; Yamori, T. Antiangiogenic effect of ZSTK474, a novel phosphatidylinositol 3-kinase inhibitor. Eur. J. Cancer, 2009, 45(5), 857-865.
[http://dx.doi.org/10.1016/j.ejca.2008.12.007] [PMID: 19144509]
[63]
Rewcastle, G.W.; Gamage, S.A.; Flanagan, J.U.; Frederick, R.; Denny, W.A.; Baguley, B.C.; Kestell, P.; Singh, R.; Kendall, J.D.; Marshall, E.S.; Lill, C.L.; Lee, W.J.; Kolekar, S.; Buchanan, C.M.; Jamieson, S.M.F.; Shepherd, P.R. Synthesis and biological evaluation of novel analogues of the pan class I phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474). J. Med. Chem., 2011, 54(20), 7105-7126.
[http://dx.doi.org/10.1021/jm200688y] [PMID: 21882832]
[64]
Li, W.; Gao, C.; Zhao, L.; Yuan, Z.; Chen, Y.; Jiang, Y. Phthalimide conjugations for the degradation of oncogenic PI3K. Eur. J. Med. Chem., 2018, 151, 237-247.
[http://dx.doi.org/10.1016/j.ejmech.2018.03.066] [PMID: 29625382]
[65]
Pinson, J.A.; Zheng, Z.; Miller, M.S.; Chalmers, D.K.; Jennings, I.G.; Thompson, P.E. L-Aminoacyl-triazine derivatives are isoform-selective PI3Kβ inhibitors that target non-conserved Asp862 of PI3Kβ. ACS Med. Chem. Lett., 2013, 4(2), 206-210.
[http://dx.doi.org/10.1021/ml300336j] [PMID: 23795239]
[66]
Balaha, M.F.; El-Hamamsy, M.H.; El-Din, N.A.E.S.S. Exploring the cytotoxicity of 1,3,5-triazines and triazine analogs against lung cancer by QSAR study using genetic function approximation. Pharma Chem., 2016, 8(3), 180-188.
[67]
Matsuno, T.; Karo, M.; Sasahara, H.; Watanabe, T.; Inaba, M.; Takahashi, M.; Yaguchi, S.I.; Yoshioka, K.; Sakato, M.; Kawashima, S. Synthesis and antitumor activity of benzimidazolyl-1,3,5-triazine and benzimidazolylpyrimidine derivatives. Chem. Pharm. Bull. (Tokyo), 2000, 48(11), 1778-1781.
[http://dx.doi.org/10.1248/cpb.48.1778] [PMID: 11086914]
[68]
Zask, A.; Verheijen, J.C.; Richard, D.J.; Kaplan, J.; Curran, K.; Toral-Barza, L.; Lucas, J.; Hollander, I.; Yu, K. Discovery of 2-ureidophenyltriazines bearing bridged morpholines as potent and selective ATP-competitive mTOR inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(8), 2644-2647.
[http://dx.doi.org/10.1016/j.bmcl.2010.02.045] [PMID: 20227881]
[69]
Peterson, E.A.; Andrews, P.S.; Be, X.; Boezio, A.A.; Bush, T.L.; Cheng, A.C.; Coats, J.R.; Colletti, A.E.; Copeland, K.W.; DuPont, M.; Graceffa, R.; Grubinska, B.; Harmange, J.C.; Kim, J.L.; Mullady, E.L.; Olivieri, P.; Schenkel, L.B.; Stanton, M.K.; Teffera, Y.; Whittington, D.A.; Cai, T.; La, D.S. Discovery of triazine-benzimidazoles as selective inhibitors of mTOR. Bioorg. Med. Chem. Lett., 2011, 21(7), 2064-2070.
[http://dx.doi.org/10.1016/j.bmcl.2011.02.007] [PMID: 21376583]
[70]
Kumar, G.J.; Kumar, S.N.; Thummuri, D.; Adari, L.B.S.; Naidu, V.G.M.; Srinivas, K.; Rao, V.J. Synthesis and characterization of new s-triazine bearing benzimidazole and benzothiazole derivatives as anticancer agents. Med. Chem. Res., 2015, 24, 3991-4001.
[http://dx.doi.org/10.1007/s00044-015-1430-9]
[71]
Guntuku, L.; Gangasani, J.K.; Thummuri, D.; Borkar, R.M.; Manavathi, B.; Ragampeta, S.; Vaidya, J.R.; Sistla, R.; Vegi, N.G.M. IITZ-01, a novel potent lysosomotropic autophagy inhibitor, has single-agent antitumor efficacy in triple-negative breast cancer in vitro and in vivo. Oncogene, 2019, 38(4), 581-595.
[http://dx.doi.org/10.1038/s41388-018-0446-2] [PMID: 30166591]
[72]
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]
[73]
Huang, Q.; Fu, Q.; Liu, Y.; Bai, J.; Wang, Q.; Liao, H.; Gong, P. 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), 257-265.
[http://dx.doi.org/10.1007/s40242-014-3253-5]
[74]
Van Dort, M.E.; Hong, H.; Wang, H.; Nino, C.A.; Lombardi, R.L.; Blanks, A.E.; Galbán, S.; Ross, B.D. Discovery of bifunctional oncogenic target inhibitors against allosteric mitogen-activated protein kinase (MEK1) and phosphatidylinositol 3-kinase (PI3K). J. Med. Chem., 2016, 59(6), 2512-2522.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01655] [PMID: 26943489]
[75]
Yu, Z.; Chen, Z.; Su, Q.; Ye, S.; Yuan, H.; Kuai, M.; Lv, M.; Tu, Z.; Yang, X.; Liu, R.; Hu, G.; Li, Q. Dual inhibitors of RAF-MEK-ERK and PI3K-PDK1-AKT pathways: Design, synthesis and preliminary anticancer activity studies of 3-substituted-5-(phenylamino) indolone derivatives. Bioorg. Med. Chem., 2019, 27(6), 944-954.
[http://dx.doi.org/10.1016/j.bmc.2019.01.028] [PMID: 30777660]
[76]
Van Dort, M.E.; Galbán, S.; Nino, C.A.; Hong, H.; Apfelbaum, A.A.; Luker, G.D.; Thurber, G.M.; Atangcho, L.; Besirli, C.G.; Ross, B.D. Structure-guided design and initial studies of a bifunctional MEK/PI3K inhibitor (ST-168). ACS Med. Chem. Lett., 2017, 8(8), 808-813.
[http://dx.doi.org/10.1021/acsmedchemlett.7b00111] [PMID: 28835793]
[77]
Liu, P.; Chen, X.; Zhu, J.; Li, B.; Chen, Z.; Wang, G.; Sun, H.; Xu, Z.; Zhao, Z.; Zhou, C.; Xie, C.; Lou, L.; Zhu, W. Design, synthesis and pharmacological evaluation of novel Hsp90N-terminal inhibitors without induction of heat shock response. ChemistryOpen, 2019, 8(3), 344-353.
[http://dx.doi.org/10.1002/open.201900055] [PMID: 30976475]
[78]
Dao, P.; Smith, N.; Scott-Algara, D.; Garbay, C.; Herbeuval, J.P.; Chen, H. Restoration of TRAIL-induced apoptosis in resistant human pancreatic cancer cells by a novel FAK inhibitor, PH11. Cancer Lett., 2015, 360(1), 48-59.
[http://dx.doi.org/10.1016/j.canlet.2015.02.016] [PMID: 25684663]
[79]
Saczewski, F.; Maruszak, M.; Bednarski, P.J. Synthesis and cytotoxic activity of imidazo[1,2-a]-1,3,5-triazine analogues of 6-mercaptopurine. Arch. Pharm. (Weinheim), 2008, 341(2), 121-125.
[http://dx.doi.org/10.1002/ardp.200700176] [PMID: 18186543]
[80]
Dao, P.; Smith, N.; Tomkiewicz-Raulet, C.; Yen-Pon, E.; Camacho-Artacho, M.; Lietha, D.; Herbeuval, J.P.; Coumoul, X.; Garbay, C.; Chen, H. Design, synthesis, and evaluation of novel imidazo[1,2-a][1,3,5]triazines and their derivatives as focal adhesion kinase inhibitors with antitumor activity. J. Med. Chem., 2015, 58(1), 237-251.
[http://dx.doi.org/10.1021/jm500784e] [PMID: 25180654]
[81]
Ganguly, S.; Jacob, S.K. Therapeutic outlook of pyrazole analogs: A mini review. Mini Rev. Med. Chem., 2017, 17(11), 959-983.
[http://dx.doi.org/10.2174/1389557516666151120115302] [PMID: 26586126]
[82]
Liu, J.J.; Zhao, M.Y.; Zhang, X.; Zhao, X.; Zhu, H.L. Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents. Mini Rev. Med. Chem., 2013, 13(13), 1957-1966.
[http://dx.doi.org/10.2174/13895575113139990078] [PMID: 23937232]
[83]
Chauhan, S.; Paliwal, S.; Chauhan, R. Anticancer activity of pyrazole via different biological mechanisms. Synth. Commun., 2014, 44, 1333-1374.
[http://dx.doi.org/10.1080/00397911.2013.837186]
[84]
Dugar, S.; Hollinger, F.P.; Mahajan, D.; Sen, S.; Kuila, B.; Arora, R.; Pawar, Y.; Shinde, V.; Rahinj, M.; Kapoor, K.K.; Bhumkar, R.; Rai, S.; Kulkarni, R. Discovery of novel and orally bioavailable inhibitors of PI3 kinase based on indazole substituted morpholino-triazines. ACS Med. Chem. Lett., 2015, 6(12), 1190-1194.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00322] [PMID: 26713102]
[85]
Farooq, M.; Sharma, A.; Almarhoon, Z.; Al-Dhfyan, A.; El-Faham, A.; Taha, N.A.; Wadaan, M.A.M.; Torre, B.G.; Albericio, F. Design and synthesis of mono-and di-pyrazolyl-s-triazine derivatives, their anticancer profile in human cancer cell lines, and in vivo toxicity in zebrafish embryos. Bioorg. Chem., 2019, 87, 457-464.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.063] [PMID: 30927586]
[86]
Peterson, E.A.; Boezio, A.A.; Andrews, P.S.; Boezio, C.M.; Bush, T.L.; Cheng, A.C.; Choquette, D.; Coats, J.R.; Colletti, A.E.; Copeland, K.W.; DuPont, M.; Graceffa, R.; Grubinska, B.; Kim, J.L.; Lewis, R.T.; Liu, J.; Mullady, E.L.; Potashman, M.H.; Romero, K.; Shaffer, P.L.; Stanton, M.K.; Stellwagen, J.C.; Teffera, Y.; Yi, S.; Cai, T.; La, D.S. Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(15), 4967-4974.
[http://dx.doi.org/10.1016/j.bmcl.2012.06.033] [PMID: 22765895]
[87]
Popowycz, F.; Schneider, C.; Debonis, S.; Skoufias, D.A.; Kozielski, F.; Galmarini, C.M.; Joseph, B. Synthesis and antiproliferative evaluation of pyrazolo[1,5-a]-1,3,5-triazine myoseverin derivatives. Bioorg. Med. Chem., 2009, 17(9), 3471-3478.
[http://dx.doi.org/10.1016/j.bmc.2009.03.007] [PMID: 19349183]
[88]
Nie, Z.; Perretta, C.; Erickson, P.; Margosiak, S.; Almassy, R.; Lu, J.; Averill, A.; Yager, K.M.; Chu, S. Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2. Bioorg. Med. Chem. Lett., 2007, 17(15), 4191-4195.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.041] [PMID: 17540560]
[89]
Cozza, G. The development of CK2 inhibitors: From traditional pharmacology to in Silico rational drug design Pharmaceuticals, 2017, 10(1-23) e26
[90]
Lim, F.P.L.; Dolzhenko, A.V. 4-Amino-substituted pyrazolo[1,5-a][1,3,5]triazin-2-amines: A new practical synthesis and biological activity. Tetrahedron Lett., 2014, 55, 6684-6688.
[http://dx.doi.org/10.1016/j.tetlet.2014.10.057]
[91]
Lim, F.P.L.; Kow, K.K.; Yeo, E.H.; Chow, S.C.; Dolzhenko, A.V. Synthesis and antileukemic activity of new fluorinated 5-aza-9-deazapurines. Heterocycles, 2016, 92, 1121-1131.
[http://dx.doi.org/10.3987/COM-16-13464]
[92]
Nie, Z.; Perretta, C.; Erickson, P.; Margosiak, S.; Lu, J.; Averill, A.; Almassy, R.; Chu, S. 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), 619-623.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.074] [PMID: 18055206]
[93]
Smolnikov, S. A.; Gorgopina, E. V.; Lezhnyova, V. R.; Ong, G. E. T.; Chui, W. K.; Dolzhenko, 4-Phenethylthio-2-phenylpyrazolo[1,5-a][1,3,5]triazin-7(6H)-one. Molbank, 2017, 2017(1-5), M970.
[94]
Bera, H.; Ojha, Pk.; Tan, B.J.; Sun, L.; Dolzhenko, A.V.; Chui, W.K.; Chiu, G.N.C. Discovery of mixed type thymidine phosphorylase inhibitors endowed with antiangiogenic properties: synthesis, pharmacological evaluation and molecular docking study of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones. Part II. Eur. J. Med. Chem., 2014, 78, 294-303.
[http://dx.doi.org/10.1016/j.ejmech.2014.03.063] [PMID: 24686016]
[95]
Aly, H.M. Novel pyrrolidinone and pyrazolo[1,5-a][1,3,5]triazine derivatives bearing a biologically active sulfamoyl moiety as a new class of antitumor agents. Monatsh. Chem., 2011, 142, 935-941.
[http://dx.doi.org/10.1007/s00706-011-0517-3]
[96]
Sun, L.; Li, J.; Bera, H.; Dolzhenko, A.V.; Chiu, G.N.C.; Chui, W.K. Fragment-based approach to the design of 5-chlorouracil-linked-pyrazolo[1,5-a][1,3,5]triazines as thymidine phosphorylase inhibitors. Eur. J. Med. Chem., 2013, 70, 400-410.
[http://dx.doi.org/10.1016/j.ejmech.2013.10.022] [PMID: 24177367]
[97]
Sun, D.; Melman, G.; Letourneau, N.J.; Hays, A.M.; Melman, A. Synthesis and antiproliferating activity of iron chelators of hydroxyamino-1,3,5-triazine family. Bioorg. Med. Chem. Lett., 2010, 20(2), 458-460.
[http://dx.doi.org/10.1016/j.bmcl.2009.11.130] [PMID: 20005708]
[98]
Moreno, L. M.; Quiroga, J.; Abonia, R.; Ramirez-Prada, J.; Insuasty, B. Synthesis of new 1,3,5-triazine-based 2-pyrazolines as potential anticancer agents. Molecules, 2018, 23(1-20) e1956
[99]
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), 709-720.
[http://dx.doi.org/10.1016/S0223-5234(02)01379-X] [PMID: 12350288]
[100]
Sharma, D.; Malhotra, A.; Bansal, R. An overview of discovery of thiazole containing heterocycles as potent GSK-3β inhibitors. Curr. Drug Discov. Technol., 2018, 15(3), 229-235.
[http://dx.doi.org/10.2174/1570163815666180104120857] [PMID: 29299988]
[101]
Peng, F.W.; Liu, D.K.; Zhang, Q.W.; Xu, Y.G.; Shi, L. VEGFR-2 inhibitors and the therapeutic applications thereof: a patent review (2012-2016). Expert Opin. Ther. Pat., 2017, 27(9), 987-1004.
[102]
de Siqueira, L.R.P.; de Moraes Gomes, P.A.T.; de Lima Ferreira, L.P.; de Melo Rêgo, M.J.B.; Leite, A.C.L. Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues. Eur. J. Med. Chem., 2019, 170, 237-260.
[http://dx.doi.org/10.1016/j.ejmech.2019.03.024] [PMID: 30904782]
[103]
Gümüş, M.; Yakan, M.; Koca, İ. Recent advances of thiazole hybrids in biological applications. Future Med. Chem., 2019, 11(15), 1979-1998.
[http://dx.doi.org/10.4155/fmc-2018-0196] [PMID: 31517529]
[104]
Ayati, A.; Emami, S.; Asadipour, A.; Shafiee, A.; Foroumadi, A. Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery. Eur. J. Med. Chem., 2015, 97, 699-718.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.015] [PMID: 25934508]
[105]
Stauffer, F.; Holzer, P.; García-Echeverría, C. Blocking the PI3K/PKB pathway in tumor cells. Curr. Med. Chem. Anticancer Agents, 2005, 5(5), 449-462.
[http://dx.doi.org/10.2174/1568011054866937] [PMID: 16178772]
[106]
Ayati, A.; Emami, S.; Moghimi, S.; Foroumadi, A. Thiazole in the targeted anticancer drug discovery. Future Med. Chem., 2019, 11(15), 1929-1952.
[http://dx.doi.org/10.4155/fmc-2018-0416] [PMID: 31313595]
[107]
Wang, X.; Yi, Y.; Lv, Q.; Zhang, J.; Wu, K.; Wu, W.; Zhang, W. Novel 1,3,5-triazine derivatives exert potent anti-cervical cancer effects by modulating Bax, Bcl2 and Caspases expression. Chem. Biol. Drug Des., 2018, 91(3), 728-734.
[http://dx.doi.org/10.1111/cbdd.13133] [PMID: 29068538]
[108]
Balaha, M.F.; El-Hamamsy, M.H.; El-Din, N.A.S.; El-Mahdy, N.A. Synthesis, evaluation and docking study of 1, 3, 5-triazine derivatives as cytotoxic agents against lung cancer. J. Appl. Pharm. Sci., 2016, 6, 28-45.
[http://dx.doi.org/10.7324/JAPS.2016.60405]
[109]
Al-Khodir, F.A.I.; Al-Warhi, T.; Abumelha, H.M.A.; Al-Issa, S.A. Synthesis, chemical and biological investigations of new Ru(III) and Se(IV) complexes containing 1,3,5-triazine chelating derivatives. J. Mol. Struct., 2019, 1179, 795-808.
[http://dx.doi.org/10.1016/j.molstruc.2018.11.082]
[110]
Qi, Z.Y.; Hao, S.Y.; Tian, H.Z.; Bian, H.L.; Hui, L.; Chen, S.W. Synthesis and biological evaluation of 1-(benzofuran-3-yl)-4-(3,4,5-trimethoxyphenyl)-1H-1,2,3-triazole derivatives as tubulin polymerization inhibitors. Bioorg. Chem., 2020, 94, 103392
[http://dx.doi.org/10.1016/j.bioorg.2019.103392] [PMID: 31669093]
[111]
Zhang, J.; Wang, S.; Ba, Y.; Xu, Z. 1,2,4-Triazole-quinoline/quinolone hybrids as potential anti-bacterial agents. Eur. J. Med. Chem., 2019, 174, 1-8.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.033] [PMID: 31015103]
[112]
Akhtar, J.; Khan, A.A.; Ali, Z.; Haider, R.; Shahar Yar, M. Structure-activity relationship (SAR) study and design strategies of nitrogen-containing heterocyclic moieties for their anticancer activities. Eur. J. Med. Chem., 2017, 125, 143-189.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.023] [PMID: 27662031]
[113]
Kaur, P.; Chawla, A. Recent developments on 1,2,4-triazole nucleus in anticancer compounds: A review. Int. Res. J. Pharm., 2017, 8, 10-29.
[http://dx.doi.org/10.7897/2230-8407.087112]
[114]
Vineberg, J.G.; Zuniga, E.S.; Kamath, A.; Chen, Y.J.; Seitz, J.D.; Ojima, I. Design, synthesis, and biological evaluations of tumor-targeting dual-warhead conjugates for a taxoid-camptothecin combination chemotherapy. J. Med. Chem., 2014, 57(13), 5777-5791.
[http://dx.doi.org/10.1021/jm500631u] [PMID: 24901491]
[115]
Lee, C.; Lo, S.T.; Lim, J.; da Costa, V.C.; Ramezani, S.; Öz, O.K.; Pavan, G.M.; Annunziata, O.; Sun, X.; Simanek, E.E. Design, synthesis and biological assessment of a triazine dendrimer with approximately 16 Paclitaxel groups and 8 PEG groups. Mol. Pharm., 2013, 10(12), 4452-4461.
[http://dx.doi.org/10.1021/mp400290u] [PMID: 24134039]
[116]
Joshi, P.; Tripathi, M.; Rawat, D.S. Synthesis and characterization of novel 1,2,3-triazole-linked theophylline and coumarin s-triazines. Indian J. Chem., 2014, 53B, 311-318.
[117]
Malah, T.E.; Nour, H.F.; Nayl, A.A.; Elkhashab, R.A.; Abdel-Megeid, F.M.E.; Ali, M.M. Anticancer evaluation of tris(triazolyl)triazine derivatives generated via click chemistry. Aust. J. Chem., 2016, 69, 905-910.
[http://dx.doi.org/10.1071/CH16006]
[118]
Bekircan, O.; Küxük, M.; Kahveci, B.; Kolayli, S. Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents. Arch. Pharm. (Weinheim), 2005, 338(8), 365-372.
[http://dx.doi.org/10.1002/ardp.200400964] [PMID: 16041836]
[119]
Dolzhenko, A.V.; Tan, B.J.; Chiu, G.N.C.; Chui, W.K.; Dolzhenko, A.V. Synthesis and biological activity of fluorinated 7-benzylamino-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-amines. J. Fluor. Chem., 2015, 175, 68-72.
[http://dx.doi.org/10.1016/j.jfluchem.2015.03.010]
[120]
Bera, H.; Dolzhenko, A.V.; Sun, L.; Dutta Gupta, S.; Chui, W.K. Synthesis and in vitro evaluation of 1,2,4-triazolo[1,5-a][1,3,5]triazine derivatives as thymidine phosphorylase inhibitors. Chem. Biol. Drug Des., 2013, 82(3), 351-360.
[http://dx.doi.org/10.1111/cbdd.12171] [PMID: 23758794]
[121]
Bera, H.; Tan, B.J.; Sun, L.; Dolzhenko, A.V.; Chui, W.K.; Chiu, G.N.C. A structure-activity relationship study of 1,2,4-triazolo[1,5-a][1,3,5]triazin-5,7-dione and its 5-thioxo analogues on anti-thymidine phosphorylase and associated anti-angiogenic activities. Eur. J. Med. Chem., 2013, 67, 325-334.
[http://dx.doi.org/10.1016/j.ejmech.2013.06.051] [PMID: 23871912]
[122]
Kaur, A.; Wakode, S.; Pathak, D.P. Benzoxazole: The molecule of diverse pharmacological importance. Int. J. Pharm. Pharm. Sci., 2015, 7(1), 16-23.
[123]
Demmer, C.S.; Bunch, L. Benzoxazoles and oxazolopyridines in medicinal chemistry studies. Eur. J. Med. Chem., 2015, 97, 778-785.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.064] [PMID: 25487760]
[124]
Sesai, S.; Desai, V.; Shingade, S. In-vitro Anti-cancer assay and apoptotic cell pathway of newly synthesized benzoxazole-Nheterocyclic hybrids as potent tyrosine kinase inhibitors. Bioorg. Med., 2020, 94, e103382
[125]
Romeo, G.; Prezzavento, O.; Intagliata, S.; Pittalà, V.; Modica, M.N.; Marrazzo, A.; Turnaturi, R.; Parenti, C.; Chiechio, S.; Arena, E.; Campisi, A.; Sposito, G.; Salerno, L. Synthesis, in vitro and in vivo characterization of new benzoxazole and benzothiazole-based sigma receptor ligands. Eur. J. Med. Chem., 2019, 174, 226-235.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.056] [PMID: 31042618]
[126]
Kumar, G.J.; Bomma, H.V.S.S.; Srihari, E.; Shrivastava, S.; Naidu, V.G.M.; Srinivas, K.; Rao, V.J. Synthesis and anticancer activity of some new s-triazine derivatives. Med. Chem. Res., 2013, 22, 5973-5981.
[http://dx.doi.org/10.1007/s00044-013-0584-6]


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VOLUME: 20
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Year: 2020
Published on: 21 July, 2020
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DOI: 10.2174/1568026620666200310122741
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