Generic placeholder image

Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

A Review on the Antitumor Activity of Various Nitrogenous-based Heterocyclic Compounds as NSCLC Inhibitors

Author(s): Jia-Chun Liu, Suresh Narva, Kang Zhou and Wen Zhang*

Volume 19, Issue 18, 2019

Page: [1517 - 1530] Pages: 14

DOI: 10.2174/1389557519666190312152358

Price: $65


At present, cancers have been causing deadly fears to humans and previously unpredictable losses to health. Especially, lung cancer is one of the most common causes of cancer-related mortality accounting for approximately 15% of all cancer cases worldwide. While Non-Small Cell Lung Carcinomas (NSCLCs) makes up to 80% of lung cancer cases. The patient compliance has been weakening because of serious drug resistance and adverse drug effects. Therefore, there is an urgent need for the development of novel structural agents to inhibit NSCLCs. Nitrogen-containing heterocyclic compounds exhibit wide range of biological properties, especially antitumor activity. We reviewed some deadly defects of clinical medicines for the lung cancer therapy and importance of nitrogen based heterocyclic derivatives against NSCLCs. Nitrogen heterocycles exhibit significant antitumor activity against NSCLCs. Nitrogen heterocyclic hybrids could be developed as multi-target-directed NSCLC inhibitors and it is believed that the review is significant for rational designs and new ideas in the development of nitrogen heterocyclic-based drugs.

Keywords: Anti tumor, lung cancer, drug resistance, nitrogen heterocyclic compounds, NSCLC inhibitors, SCLCs.

Graphical Abstract
Chen, W.Q.; Zheng, R.S.; Baade, P.D.; Zhang, S.W.; Zeng, H.M.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Cancer statistics in china 2015. CA Cancer J. Clin., 2016, 66, 115-132.
WHO. Cancer Fact Sheet; World Health Organization, 2011.
Jemal, A.; Center, M.M.; DeSantis, C.; Ward, E.M. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol. Biomarkers Prev., 2010, 19, 1893-1907.
Parkin, D.M.; Bray, F.; Ferlay, J.; Pisani, P. Global cancer statistics 2002. CA Cancer J. Clin., 2005, 55, 74-108.
Tyczynski, J.E.; Bray, F.; Parkin, D.M. Lung cancer in europe in 2000: Epidemiology, prevention, and early detection. Lancet Oncol., 2003, 4, 45-55.
Youlden, D.R.; Cramb, S.M.; Baade, P.D. The international epidemiology of lung cancer: Geographical distribution and secular trends. J. Thorac. Oncol., 2008, 3, 819-831.
Toh, C.K. The changing epidemiology of lung cancer. Methods Mol. Biol., 2009, 472, 397-411.
Anna, Z.; Boris, Z. miRNAs in lung cancer: A link to aging. Ageing Res. Rev., 2014, 17, 54-67.
Wood, S.L.; Pernemalm, M.; Crosbi, P.A.; Whetton, A.D. The role of the tumor-microenvironment in lung cancer-metastasis andits relationship to potential therapeutic targets. Cancer Treat. Rev., 2014, 40, 558-566.
Hoffman, P.C.; Mauer, A.M.; Vokes, E.E. Lung cancer. Lancet, 2000, 355, 479-485.
Youlden, D.R.; Cramb, S.M.; Baade, P.D. The International Epidemiology of Lung Cancer: Geographical distribution and secular trend. J. Thorac. Oncol., 2008, 8, 819-831.
Stahel, R.; Thatcher, N.; Früh, M.; Le Pechoux, C.; Postmus, P.E.; Sorensen, J.B.; Felip, E. 1st ESMO Consensus Conference in lung cancer; Lugano 2010: Small-cell lung cancer. Ann. Oncol., 2011, 22, 1973-1980.
Raungrut, P.; Wongkotsila, A.; Lirdprapamongkol, K.; Svasti, J.; Geater, S.L.; Phukaoloun, M.; Suwiwat, S.; Thongsuksai, P. Prognostic significance of 14-3-3gamma overexpression in advanced non-small cell lung cancer. Asian Pac. J. Cancer Prev., 2014, 15, 3513-3518.
Hou, Z.B.; Zhao, W.; Zhou, J.; Shen, L.; Zhan, P.; Xu, C.H.; Chang, C.J.; Bi, H.; Zou, J.; Yao, X.; Huange, R.M.; Yu, L.; Yan, J. A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival. Int. J. Biochem. Cell Biol., 2014, 53, 380-388.
Liao, Z.; Lin, S.H.; Cox, J.D. Status of particle therapy for lung cancer. Acta Oncol., 2011, 50, 745-756.
Liseth, L.; Berg, V.D.; Klinkenberg, T.J.; Groen, H.J.M.; Widder, J. Patterns of recurrence and survival after surgery or stereotactic radiotherapy for early stage NSCLC. J. Thorac. Oncol., 2015, 10, 826-831.
Husain, Z.A.; Anthony, W.K.; James, B.Y.; Decker, R.H.; Corso, C.D. Defining the high-risk population for mortality after resection of early stage NSCLC. Clin. Lung Cancer, 2015, 16, 183-187.
Schytte, T.; Bentzen, S.M.; Brink, C.; Hansen, O. Radiation induced lung damage: Changes in pulmonary function after definitive radiotherapy for NSCLC. Radiother. Oncol., 2015, 117, 23-28.
Narang, H.; Kumar, A.; Bhat, N.; Pandey, B.N.; Ghosh, A. Effect of proton and gamma irradiation on human lung carcinoma cells: Gene expression, cell cycle, cell death, epithelial-mesenchymal transition and cancer-stem cell trait as biological end points. Mutat. Res., 2015, 780, 35-46.
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
Zenke, Y.; Umemura, S.; Sugiyama, E.; Kirita, K.; Matsumoto, S.; Yoh, K.; Niho, S.J.; Ohmatsu, H.; Goto, K. Successful treatment with afatinib after grade 3 hepatotoxicity induced by both gefitinib and erlotinib in EGFR mutation-positive non-small cell lung cancer. Lung Cancer, 2016, 99, 1-3.
Takeda, M.; Okamoto, I.; Nakagawa, K. Pooled safety analysis of EGFR-TKI treatment for EGFR mutation-positive non-small cell lung cancer. Lung Cancer, 2015, 88, 74-79.
Kouranos, V.; Dimopoulos, G.; Vassias, A.; Syrigos, K.N. Chemotherapy-induced neutropenia in lung cancer patients: The role of antibiotic prophylaxis. Cancer Lett., 2011, 313, 9-14.
Siegel, R.; Naishadham, D.; Jemal, A. Cancer statistics. CA Cancer J. Clin., 2013, 63, 11-30.
Varlotto, J.M.; Medford-Davis, L.N.; Recht, A.; Flickinger, J.C.; Schaefer, E.; DeCamp, M.M. Failure rates and patterns of recurrence in patients with respected N1 non-small-cell lung cancer. Int. J. Radiat. Oncol. Biol. Phys., 2011, 81, 353-359.
Maeng, H.J.; Lee, W.J.; Jin, Q.R.; Chang, J.E.; Shim, W.S. Upregulation of COX-2 in the lung cancer promotes over expression of multidrug resistance protein 4 (MRP4) via PGE2-dependent pathway. Eur. J. Pharm. Sci., 2014, 62, 189-196.
Kobayashi, S.; Boggon, T.J.; Dayaram, T.; Janne, P.A.; Kocher, O.; Meyerson, M.; Johnson, B.E.; Eck, M.J.; Tenen, D.G.; Halmos, B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N. Engl. J. Med., 2005, 352, 786-792.
Engelman, J.A.; Zejnullahu, K.; Mitsudomi, T.; Song, Y.; Hyland, C.; Park, J.O.; Lindeman, N.; Gale, C.M.; Zhao, X.; Christensen, J.; Kosaka, T.; Holmes, A.J.; Rogers, A.M.; Cappuzzo, F.; Mok, T.; Lee, C.; Johnson, B.E.; Cantley, L.C.; Janne, P.A. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science, 2007, 316, 1039-1043.
Dasari, S.; Tchounwou, P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol., 2014, 740, 364-378.
Zheng, W.J.; Cao, C.W.; Liu, Y.N.; Yu, Q.Q.; Zheng, C.P.; Sun, D.D.; Ren, X.F.; Liu, J. Multifunctional polyamidoamine-modified selenium nanoparticles dual-delivering siRNA and cisplatin to A549/DDP cells for reversal multidrug resistance. Acta Biomater., 2015, 11, 368-380.
Li, Y.Y.; Lam, S.K.; Mak, J.C.W.; Zheng, C.Y.; Ho, J.C.M. Erlotinib-induced autophagy in epidermal growth factor receptor mutated non-small cell lung cancer. Lung Cancer, 2013, 81, 354-361.
Watz, H.; Barnacle, H.; Hartley, B.F.; Chan, M.M.R. Efficacy and safety of the p38 MAPK inhibitor losmapimod for patients with chronic obstructive pulmonary disease: A randomised, double-blind, placebo-controlled trial. Lancet Respir. Med., 2014, 2, 63-72.
Wilson, T.R.; Fridlyand, J.; Yan, Y.B.; Penuel, E.; Burton, L.; Chan, E.; Peng, J.; Lin, E.; Wang, Y.L.; Sosman, J.; Ribas, A.; Li, J.; Moffat, J.; Sutherlin, D.P.; Koeppen, H.; Merchant, M.; Neve, R.; Settleman, J. Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature, 2012, 487, 505-509.
Elzahabi, H.S.A. Synthesis, characterization of some benzazoles bearing pyridine moiety: Search for novel anticancer agents. Eur. J. Med. Chem., 2011, 46, 4025-4034.
Jiao, Y.; Xin, B.T.; Zhang, Y.M.; Wu, J.B.; Lu, X.L.; Zheng, Y.; Tang, W.F.; Zhou, X. Design, synthesis and evaluation of novel 2-(1H-imidazol-2-yl)pyridine Sorafenib derivatives as potential BRAF inhibitors and anti-tumor agents. Eur. J. Med. Chem., 2015, 90, 170-183.
Qin, M.Z.; Zhai, X.; Xie, H.B.; Ma, J.J.; Lu, K.; Wang, Y.; Wang, L.H.; Gu, Y.C.; Gong, P. Design and synthesis of novel 2-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridines as potential antitumor agents. Eur. J. Med. Chem., 2014, 81, 47-58.
Rastogi, S.; Rajanna, A.; Webb, G.; Chhabra, B.; Foster, B.; Webb, N. Puri. Mechanism of c-Met and EGFR tyrosine kinase inhibitor resistance through epithelial mesenchymal transition in non-small cell lung cancer. Biochem. Biophys. Res. Commun., 2016, 477, 937-944.
Liu, N.; Wang, Y.F.; Huang, G.C.; Ji, C.H.; Fan, W.; Li, H.T.; Cheng, Y.; Tian, H.Q. Design, synthesis and biological evaluation of 1H-pyrrolo[2,3-b]pyridine and 1H-pyrazolo[3,4-b]pyridine derivatives as c-Met inhibitors. Bioorg. Chem., 2016, 65, 146-158.
Stravopodis, D.J.; Margaritis, L.H.; Voutsinas, G.E. Drug-mediated targeted disruption of multiple protein activities through functional inhibition of the Hsp90 chaperone complex. Curr. Med. Chem., 2007, 14, 3122-3138.
Whitesell, L.; Lindquist, S.L. HSP90 and the chaperoning of cancer. Nat. Rev. Cancer, 2005, 5, 761-772.
Kamal, A.; Thao, L.; Sensintaffar, J.; Zhang, L.; Boehm, M.F.; Fritz, L.C.; Burrows, F.J. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature, 2003, 425, 407-410.
Sequist, L.V.; Gettinger, S.; Senzer, N.N.; Martins, R.G.; Jänne, P.A.; Lilenbaum, R.; Gray, J.E.; Iafrate, A.J.; Katayama, R.; Hafeez, N.; Sweeney, J.; Walker, J.R.; Fritz, C.; Ross, R.W.; Grayzel, D.; Engelman, J.A.; Borger, D.R.; Paez, G.; Natale, R. Activity of IPI-504, a Novel Heat-Shock Protein 90 Inhibitor, in Patients With Molecularly Defined Non–Small-Cell Lung Cancer. J. Clin. Oncol., 2010, 28, 4953-4960.
Garon, E.B.; Finn, R.S.; Hamidi, H.; Dering, J.; Pitts, S.; Kamranpour, N.; Desai, A.J.; Hosmer, W.; Ide, S.; Avsar, E.; Jensen, M.R.; Quadt, C.; Liu, M.; Dubinett, S.M.; Slamon, D.J. The HSP90 inhibitor NVP-AUY922 potently inhibits non–small cell lung cancer growth. Mol. Cancer Ther., 2013, 12, 890-900.
Baruchello, R.; Simoni, D.; Marchetti, P.; Rondanin, R.; Mangiola, S.; Costantini, C.; Meli, M.; Giannini, G.; Vesci, L.; Carollo, V.; Brunetti, T.; Battistuzzi, G.; Tolomeo, M.; Cabri, W. 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors. Eur. J. Med. Chem., 2014, 76, 53-60.
Zhu, W.F.; Wang, W.H.; Xu, S.; Tang, Q.D.; Luo, R.; Wang, M.; Gong, P.; Zheng, P.W. Design, synthesis, and docking studies of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors. Bioorg. Med. Chem., 2016, 24, 812-819.
Zhu, W.F.; Wang, W.H.; Xu, S.; Wang, J.Q.; Tang, Q.D.; Wu, C.J.; Zhao, Y.F.; Zheng, P.W. Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors. Bioorg. Med. Chem., 2016, 24, 1749-1756.
Tang, Q.D.; Wang, L.X.; Tu, Y.Y.; Zhu, W.F.; Luo, R.; Tu, Q.D.; Wang, P.; Wu, C.J.; Gong, P.; Zheng, P.W. Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors. Bioorg. Med. Chem. Lett., 2016, 26, 1680-1684.
Narva, S.; Chitti, S.; Bala, B.R.; Alvala, M.; Jain, N.; Kondapalli, V.G.C.S. Synthesis and biological evaluation of pyrrolo[2,3-b]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA. Eur. J. Med. Chem., 2016, 114, 220-231.
Anderson, M.; Beattie, J.F.; Breault, G.A.; Breed, J.; Byth, K.F.; Culshaw, J.D.; Ellston, R.P.A.; Green, S.; Minshull, C.A.; Norman, R.A.; Pauptit, R.A.; Stanway, J.; Thomas, A.P.; Jewsbury, P.J. Imidazo[1,2-a]pyridines: A potent and selective class of cyclin-dependent kinase inhibitors identified through structure-based hybridization. Bioorg. Med. Chem. Lett., 2003, 13, 3021-3026.
Byth, K.F.; Culshaw, J.D.; Green, S.; Oakes, S.E. Thomas, A.P. Imidazo[1,2-a]pyridines. Part 2: SAR and optimisation of a potent and selective class of cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. Lett., 2004, 14, 2245-2248.
Vilchis-Reyes, M.A.; Zentella, A.; Martinez-Urbina, M.A.; Guzma, A.; Vargas, O.; Ramirez, M.T. Apan; Ventura Gallegos, J.L.; Diaz, E.Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a] pyridine- and quinoline-substituted 2-aminopyrimidine derivatives. Eur. J. Med. Chem., 2010, 45, 379-386.
Sarlauskas, J.; Peciukaityte-Alksne, M.; Miseviciene, L.; Maroziene, A.; Polmickaite, E.; Staniulyte, Z.; Cenas, N.; Anusevicius, Z. Naphtho[1ʹ,2ʹ:4,5]imidazo[1,2-a]pyridine-5,6-diones: Synthesis, enzymatic reduction and cytotoxic activity. Bioorg. Med. Chem. Lett., 2016, 26, 512-517.
Hayakawa, R.; Shioya, T.; Agatsuma, H.; Furukawa, Y. Sugano, Thienopyridine and benzofuran derivatives as potent anti-tumor agents possessing different structure-activity relationships. Bioorg. Med. Chem. Lett., 2004, 14, 3411-3414.
Claridge, S.; Raeppel, F.; Granger, M.C.; Bernstein, N.; Saavedra, O.; Zhan, L.J.; Llewellyn, D.; Wahhab, A.; Deziel, R.; Rahil, N.; Beaulieu, J.; Nguyen, H.; Dupont, I.; Barsalou, A.; Beaulieu, C.; Chute, I.; Gravel, S.; Robert, M.F.; Lefebvre, S.; Dubay, M.; Pascal, R.; Gillespie, J.; Jin, Z.Y.; Wang, J.; Besterman, J.M.; MacLeod, A.R.; Vaisburg, A. Discovery of a novel and potent series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases. Bioorg. Med. Chem. Lett., 2008, 18, 2793-2798.
Queiroz, M.J.R.P.; Calhelha, R.C.; Vale-Silva, L.A.; Pinto, E.; Almeida, G.M.; Vasconcelos, M.H. Synthesis and evaluation of tumor cell growth inhibition of methyl 3-amino6-[(hetero)-arylethynyl]-thieno[3,2-b]pyridine-2-carboxylates. Structure-activity relationships, effects on the cell cycle and apoptosis. Eur. J. Med. Chem., 2011, 46, 236-240.
Queiroz, M.J.R.P.; Calhelha, R.C.; Vale-Silva, L.A.; Pinto, E.; Lima, R.T.; Vasconcelos, M.H. Efficient synthesis of 6-(hetero) arylthieno[3,2-b]pyridines by SuzukieMiyaura coupling. Evaluation of growth inhibition on human tumor cell lines, SARs and effects on the cell cycle. Eur. J. Med. Chem., 2010, 45, 5628-5634.
Queiroz, M.J.R.P.; Peixoto, D.; Calhelha, R.C.; Soares, P.; Santos, T.D.; Lima, R.T.; Campos, J.F.; Abreu, R.M.V. Ferreira Isabel, C.F.R. Vasconcelos, M.H. New di(hetero)arylethers and di(hetero)-arylamines in the thieno [3,2-b]pyridine series: Synthesis, growth inhibitory activity on human tumor cell lines and non-tumor cells, effects on cell cycle and on programmed cell death. Eur. J. Med. Chem., 2013, 69, 855-862.
Ravi, C.; Qayum, A.; Mohan, D.C.; Singh, S.K.; Adimurthy, S. Design, synthesis and cytotoxicity studies of novel pyrazolo[1, 5-a] pyridine derivatives. Eur. J. Med. Chem., 2017, 126, 277-285.
Chavva, S.; Pillalamarri, V.; Banda, S.; Gautham, J.; Gaddamedi, P.; Yedla, C.G.; Kumar, N. Banda, Synthesis and biological evaluation of novel alkyl amide functionalized trifluoromethyl substituted pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. Bioorg. Med. Chem. Lett., 2013, 23, 5893-5895.
Nagender, P.; Reddy, M.G.; Kumar, R.N.; Poornachandra, Y.; Kumar, C.G.; Narsaiah, B. Synthesis, cytotoxicity, antimicrobial and anti-biofilm activities of novel pyrazolo[3,4-b]pyridine and pyrimidine functionalized 1,2,3-triazole derivatives. Bioorg. Med. Chem. Lett., 2014, 24, 2905-2908.
Nagender, P.; Kumar, R.N.; Reddy, G.M.; Swaroop, D.K.; Poornachandra, Y.; Kumar, C.G.; Narsaiah, B. Synthesis of novel hydrazone and azole functionalized pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents. Bioorg. Med. Chem. Lett., 2016, 26, 4427-4432.
Yakes, F.M.; Chen, J.; Tan, J.; Yamaguchi, K.; Shi, Y.C.; Yu, P.W.; Qian, F.; Chu, F.; Bentzien, F.; Cancilla, B.; Orf, J.; You, A.; Laird, A.D.; Engst, S.; Lee, L.; Lesch, J.; Chou, Y.C.; Joly, A.H. Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, simultaneously suppresses Metastasis, Angiogenesis, and Tumor Growth. Mol. Cancer Ther., 2011, 10, 2298-2308.
Tseng, C.H.; Chen, Y.L.; Yang, C.L.; Cheng, C.M.; Han, C.H.; Tzeng, C.C. Synthesis of 6-substituted 9-methoxy-11H-indeno[1,2-c]quinoline-11-one derivatives as potential anticancer agents. Bioorg. Med. Chem., 2012, 20, 4397-4404.
Tseng, C.H.; Chen, Y.L.; Lu, P.J.; Yang, C.N.; Tzeng, C.C. Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives. Bioorg. Med. Chem., 2008, 16, 3153-3162.
Tseng, C.H.; Chen, Y.L.; Chung, K.Y.; Cheng, C.M.; Wang, C.H.; Tzeng, C.C. Synthesis and antiproliferative evaluation of 6-arylindeno[1,2-c]quinoline derivatives. Bioorg. Med. Chem., 2009, 17, 7465-7476.
Lu, C.M.; Chen, Y.L.; Chen, H.L.; Chen, C.A.; Lu, P.J.; Yang, C.N.; Tzeng, C.C. Synthesis and antiproliferative evaluation of certain indolo[3,2-c]quinoline derivatives. Bioorg. Med. Chem., 2010, 18, 1948-1957.
Wang, M.; Switalska, Z.W.; Mei, W.J.; Lu, Y.; Takahara, X.W.; Feng, I.E.T.; El-Sayed, J.; Wietrzyk, T. Inokuchi. Synthesis and in vitro antiproliferative activity of new 11-aminoalkylamino-substituted 5H- and 6H-indolo[2,3-b]quinolines; structure–activity relationships of neocryptolepines and 6-methyl congeners. Bioorg. Med. Chem., 2012, 20, 4820-4829.
Ghatak, S.; Raha, S. Differential alterations of positive and negative regulators of beta catenin enhance endogenous expression and activity of beta catenin in A549 non small cell lung cancer (NSCLC) cells. Genes Dis., 2016, 3, 282-288.
Yang, Y.; Liu, L.; Cai, J.C.; Wu, J.H.; Guan, H.Y.; Zhu, X.; Yuan, J.; Li, M.F. DEPDC1B enhances migration and invasion of non-small cell lung cancer cells via activating Wnt/β-catenin signaling. Biochem. Biophys. Res. Commun., 2014, 450, 899-905.
Gong, Y.D.; Dong, M.S.; Lee, S.B.; Kim, N.; Bae, M.S.; Kang, N.S. A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines. Bioorg. Med. Chem., 2011, 19, 5639-5647.
Reckamp, K.L.; Melnikova, V.O.; Karlovich, C.; Sequist, L.V.; Camidge, D.R.; Wakelee, H.; Perol, M.; Oxnard, G.R.; Kosco, K.; Croucher, P.; Samuelsz, E.; Vibat, C.R.; Guerrero, S.; Geis, J.; Berz, D.; Mann, E.; Matheny, S.; Rolfe, L.; Raponi, M.; Erlander, M.G.; Gadgeel, S. A highly sensitive and quantitative test platform for detection of NSCLC EGFR mutations in urine and plasma. J. Thorac. Oncol., 2016, 11, 1690-1700.
Kekesi, A. Sipos, G. Nemeth, J. Pato, N. Breza, F. Baska, L.Orfi, G. Keri, Synthesis and biological evaluation of novel pyrido[2,3-b]pyrazines inhibiting both erlotinib-sensitive and erlotinib-resistant cell lines. Bioorg. Med. Chem. Lett., 2013, 23, 6152-6155.
Defaux, J.; Antoine, M.; Loge, C.; Borgne, M.L.; Schuster, T.; Seipelt, I.; Aicher, B.; Teifel, M.; Günther, E.; Gerlach, M.; Marchand, P. Discovery of (7-aryl-1,5-naphthyridin-2-yl)ureas as dual inhibitors of ERK2 and Aurora B kinases with antiproliferative activity against cancer cells. Bioorg. Med. Chem. Lett., 2014, 24, 3748-3752.
Rudys, S.; Rios-Luci, C.; Perez-Roth, E.; Cikotiene, I.; Padron, J.M. Antiproliferative activity of novel benzo[b][1,6]naphthyridines in human solid tumor cell lines. Bioorg. Med. Chem. Lett., 2010, 20, 1504-1506.
Wu, J.F.; Liu, M.M.; Huang, S.X.; Wang, Y. Design and synthesis of novel substituted naphthyridines as potential c-Met kinase inhibitors based on MK-2461. Bioorg. Med. Chem. Lett., 2015, 25, 3251-3255.
Insuasty, B.; Becerra, D.; Quiroga, J.; Abonia, R.; Nogueras, M.; Cobo, J. Microwave-assisted synthesis of pyrimido[4,5-b][1,6]-naphthyridin-4(3H)-ones with potential antitumor activity. Eur. J. Med. Chem., 2013, 60, 1-9.
Alonso, C.; Fuertes, M.; Gonzalez, M.; Rubiales, G.; Tesauro, C.; Knudsen, B.R.; Palacios, F. Synthesis and biological evaluation of indeno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with antiproliferative activity. Eur. J. Med. Chem., 2016, 115, 179-190.
Kumar, V.; Jaggi, M.; Singh, A.T.; Madaan, A.; Sanna, V.; Singh, P.; Sharma, P.K.; Irchhaiya, R.; Burman, A.C. 1,8-Naphthyridine-3-carboxamide derivatives with anticancer and anti-inflammatory activity. Eur. J. Med. Chem., 2009, 44, 3356-3362.
Zhang, Y.; Zhang, K.; Zhao, M.; Zhang, L.X.; Qin, M.Z.; Guo, S.C.; Zhao, Y.F.; Gong, P. Discovery of a novel class anti-proliferative agents and potential inhibitors of EGFR tyrosine kinases based on 4-anilinotetrahydropyrido[4,3-d]pyrimidine scaffold: Design, synthesis and biological evaluations. Bioorg. Med. Chem., 2015, 23, 4591-4607.
Kumar, R.N.; Dev, G.J.; Ravikumar, N.; Swaroop, D.K.; Debanjan, B.; Bharath, G.; Narsaiah, B.; Jain, S.N.; Rao, A.G. Synthesis of novel triazole/isoxazole functionalized 7-(trifluoromethyl)pyrido-[2,3-d]pyrimidine derivatives as promising anticancer and antibacterial agents. Bioorg. Med. Chem. Lett., 2016, 26, 2927-2930.
Fares, S.M.; Abou-Seri, H.A.; Abdel-Aziz, S.E.S.; Abbas, M.M.; Youssef, R.A. Eladwy, Synthesis and antitumor activity of pyrido [2,3-d]pyrimidine and pyrido[2,3-d] [1,2,4]triazolo[4,3-a]pyrimi-dine derivatives that induce apoptosis through G1 cell-cycle arrest. Eur. J. Med. Chem., 2014, 83, 155-166.
Avendano, C.; Perez, J.M.; Blanco, M.M.; Fuente, J.A.; Manzanaro, S.; Vicent, M.J.; Martin, M.J.; Salvador-Tormo, N.; Menendez, J.C. Synthesis and structure-activity relationships of 1,5-diazaanthraquinones as antitumour compounds. Bioorg. Med. Chem. Lett., 2004, 14, 3929-3932.
Brahic, C.; Darro, F.; Belloir, M.; Bastide, J.; Kiss, R.; Delfourne, E. Synthesis and cytotoxic evaluation of analogues of the marine pyridoacridine amphimedine. Bioorg. Med. Chem., 2002, 10, 2845-2853.
Delfourne, E.; Kiss, R.; Corre, L.L.; Merza, J.; Bastide, J.; Frydman, A.; Darro, F. Synthesis and in vitro antitumor activity of an isomer of the marine pyridoacridine alkaloid ascididemin and related compounds. Bioorg. Med. Chem., 2003, 11, 4351-4356.
Delfourne, E.; Kiss, R.; Corre, L.L.; Dujols, F.; Bastide, J.; Collignon, F.; Lesur, B.; Frydman, A.; Darro, F. Synthesis and in vitro antitumor activity of ring C and D-substituted phenanthrolin-7-one derivatives, analogues of the marine pyridoacridine alkaloids ascididemin and meridine. Bioorg. Med. Chem., 2004, 12, 3987-3994.
Son, J.K.; Zhao, L.X.; Basnet, A.; Thapa, P.; Karki, R.; Na, Y.; Jahng, Y.; Jeong, T.C.; Jeong, B.S.; Lee, C.S.; Lee, E.S. Synthesis of 2,6-diaryl-substituted pyridines and their antitumor activities. Eur. J. Med. Chem., 2008, 43, 675-682.
Basnet, A.; Thapa, P.; Karki, R.; Na, Y.; Jahng, Y.; Jeong, B.S.; Jeong, T.C.; Lee, C.S.; Lee, E.S. 2,4,6-Trisubstituted pyridines: Synthesis, topoisomerase I and II inhibitory activity, cytotoxicity, and structure-activity relationship. Bioorg. Med. Chem., 2007, 15, 4351-4359.
Sangani, C.B.; Makawana, J.A.; Duan, Y.T.; Yin, Y.; Teraiya, S.B.; Thumar, N.J.; Zhu, H.L. Design, synthesis and molecular modeling of biquinoline–pyridine hybrids as a new class of potential EGFR and HER-2 kinase inhibitors. Bioorg. Med. Chem. Lett., 2014, 24, 4472-4476.
Sangani, C.B.; Makawana, J.A.; Zhang, X.; Teraiya, S.B.; Lin, L.; Zhu, H.L. Design, synthesis and molecular modeling of pyrazole-quinoline-pyridine hybrids as a new class of antimicrobial and anticancer agents. Eur. J. Med. Chem., 2014, 76, 549-557.
Sun, D.D.; Wang, W.Z.; Mao, J.W.; Mei, W.J.; Liu, J. Imidazo [4,5-f][1,10] phenanthroline derivatives as inhibitor of c-myc gene expression in A549 cells via NF-κB pathway. Bioorg. Med. Chem. Lett., 2012, 22, 102-105.
Zhang, H.; Xiang, J.F.; Hu, H.Y.; Liu, Y.; Yang, F.M.; Shen, G.; Tang, Y.L.; Chen, C.F. Selective recognition of specific G-quadruplex vs. duplex DNA by a phenanthroline derivative. Int. J. Biol. Macromol., 2015, 78, 149-156.
Huang, P.; Ao, J.P.; Zhou, L.Z.; Su, Y.; Huang, W.; Zhu, X.Y.; Yan, D.Y. Facile approach to construct ternary cocktail nanoparticles for cancer combination therapy. Bioconjug. Chem., 2016, 27, 1564-1568.
Zimmermann, G.R.; Lehar, J.; Keith, C.T. Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov. Today, 2007, 12, 34-42.

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