Chemistry and pharmacological diversity of quinoxaline motifs as anticancer agents

Open access


Surpassing heart diseases, cancer is taking the lead as the deadliest disease because of its fast rate of spreading in all parts of the world. Tireless commitment to searching for novel therapeutic medicines is a worthwhile adventure in synthetic chemistry because of the drug resistance predicament and regular outbreak of new diseases due to abnormal cell growth and proliferation. Medicinal chemistry researchers and pharmacists have unveiled quinoxaline templates as precursors of importance and valuable intermediates in drug discovery because they have been established to possess diverse pharmacological potentials. Hence, this review highlights the current versatile routes to accessing functionalized quinoxaline motifs and harnessing their documented therapeutic potentials for anticancer drug development.

1. World Health Organization, Cancer Control: Knowledge into Action. WHO Guide, Geneva 2005;; last access date November 27, 2017.

2. M. R. Alison, The Cancer Handbook, Nature Publishing Group, London 2002.

3. M. Shaharyar, M. M. Abdullah, M. A. Bakht and J. Majeed, Pyrazoline bearing benzimidazoles: Search for anticancer agent, Eur. J. Med. Chem. 45 (2010) 114–119;

4. K. M. Amin, M. M. Ismail, E. Noaman, D. H. Soliman and Y. A. Ammar, New quinoxaline 1,4-di-N-oxides. Part 1: Hypoxia-selective cytotoxins and anticancer agents derived from quinoxaline 1, 4-di-N-oxides, Bioorg. Med. Chem. 14 (2006) 6917–6923;

5. A. Courbet, N. Bec, C. Constant, C. Larroque, M. Pugniere, S. E. Messaoudi, Z. Zghaib, S. Khier, C. Deleuze-Masquefa and F. Gattacceca, Imidazoquinoxaline anticancer derivatives and imiquimod interact with tubulin: Characterization of molecular microtubule inhibiting mechansims in correlation with cytotoxicity, PLoS ONE 12 (2017) e0182022;

6. Q. Wei, H. Liu, H. Zhou, D. Zhang, Z. Zhang and Q. Zhou, Anticancer activity of a thymidine quinoxaline conjugate is modulated by cytosolic thymidine pathways, BMC Cancer 15 (2015) 159 (11 pages);

7. Q. Guan, C. Han, D. Zuo, M. Zhai, Z. Li, Q. Zhang, Y. Zhai, X. Jiang, K. Bao, Y. Wu and W. Zhang, Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities, Eur. J. Med. Chem. 87 (2014) 306–315;

8. H. K. Rim, S. Cho, D. H. Shin, K. S. Chung, Y. W. Cho, J. H. Choi, J. Y. Lee and K. Lee, T-Type Ca2+ channel blocker, KYS05090 induces autophagy and apoptosis in A549 cells through inhibiting glucose uptake, Molecules 19 (2014) 9864–9875;

9. C. H. Tseng, Y. L. Chen, P. J. Lu, C. N. Yang and C. C. Tzeng, Synthesis and antiproliferative evaluation of certain indeno[1,2-c]quinoline derivatives, Bioorg. Med. Chem. 16 (2008) 3153–3162;

10. O. O. Ajani and O. C. Nwinyi, Synthesis and evaluation of antimicrobial activity of phenyl and furan-2-yl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one and their hydrazone precursors, Can. J. Pure Appl. Sci. 3 (2009) 983–992.

11. V. M. Lakshmi, F. F. Hsu, H. A. J. Schut and T. V. Zenser, Stability and reactivity of 2-nitroso amino-3,8-dimethylimidazo[4,5-f]quinoxaline, Chem. Res. Toxicol. 19 (2006) 325–333;

12. R. B. K. Siram, J. Smith, T. D. Anthopoulos and S. Patil, Acenaphtho[1,2-b]quinoxaline based low band gap copolymers for organic thin film transistor applications, J. Mat. Chem. 22 (2012) 4450–4458;

13. O. O. Ajani, C. A. Obafemi, O. C. Nwinyi and D. A. Akinpelu, Microwave assisted synthesis and antimicrobial activity of 2-quinoxalinone-3-hydrazone derivatives, Bioorg. Med. Chem. 18 (2010) 214–221;

14. S. Srivastava, J. Banerjee and N. Srestha, Quinoxaline as a potent heterocyclic moiety, IOSR J. Pharm. 4 (2014) 17–27;

15. M. Veiraj and D. Sowmya, A review on cancer screening, Int. J. PharmTech. Res. 9 (2016) 224–233.

16. M. Ghouari, The relationship between food and cancer, Int. J. Innov. Appl. Stud. 8 (2014) 1814–1830.

17. S. Kumar, X. Peng, J. Daley, L. Yang, J. Shen, N. Nguyen, G. Bae, H. Niu, Y. Peng, H-J. Hsieh, L. Wang, C. Rao, C. C. Stephan, P. Sung, G. Ira and G. Peng, Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells, Oncogenesis 6 (2017) e319;

18. R. Derynck, B. P. Muthusamy and K. Y. Saeteurn, Signaling pathway cooperation in TGF-beta-induced epithelial-mesenchymal transition, Curr. Opin. Cell Biol. 31 (2014) 56–66;

19. J. Yin, W. Ren, X. Huang, T. Li and Y. Yin, Protein restriction and cancer, Biochim. Biophys. Acta 1869 (2018) 256–262;

20. L. Fontana, R. M. Adelaiye, A. L. Rastelli, K. M. Miles, E. Ciamporcero, V. D. Longo, H. Nguyen, R. Vessella and R. Pili, Dietary protein restriction inhibits tumor growth in human xenograft models of prostate and breast cancer, Oncotarget 4 (2013) 2451–2461;

21. S. D. Boone, K. B. Baumgartner, R. N. Baumgartner, A. E. Connor, E. M. John, A. R. Giuliano, L. M. Hines, S. N. Rai, E. C. Riley, C. M. Pinkston, R. K. Wolff and M. L. Slattery, Active and passive cigarette smoking and mortality among Hispanic and non-Hispanic white women diagnosed with invasive breast cancer, Ann. Epidemiol. 25 (2015) 824–831;

22. H. Parada, P. T. Bradshaw, S. E. Steck, L. S. Engel, K. Conway, S. L. Teitelbaum, A. I. Neugut, R. M. Santella and M. D. Gammon, Postdiagnosis changes in cigarette smoking and survival following breast cancer, JNCI Cancer Spect. 1 (2017) Article ID pkx001 (8 pages);

23. J. Connor, Alcohol consumption as a cause of cancer, Addiction 112 (2017) 222–228;

24. C. Pelucchi, I. Tramacere, P. Boffetta, E. Negri and C. La Vecchia, Alcohol consumption and cancer risk, Nutr. Cancer 63 (2011) 983–990;

25. V. Bagnardi, M. Rota, E. Botteri, I. Tramacere, F. Islami, V. Fedirko, L. Scotti, M. Jenab, F. Turati, E. Pasquali, C. Pelucchi, C. Galeone, R. Bellocco, E. Negri, G. Corrao, P. Boffetta and C. La Vecchia, Alcohol consumption and site-specific cancer risk: a comprehensive dose–response meta-analysis, Br. J. Cancer 112 (2015) 580–593;

26. P. Bofetta and L. Garfinkel, Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study, Epidemiology 1 (1990) 342–348.

27. M. Kotepui, Diet and risk of breast cancer, Contemp. Oncol. 20 (2016) 13–19;

28. R. E. Rossi, M. Pericleous, D. Mandair, T. Whyand and M. E. Caplain, The role of dietary factors in prevention and progression of breast cancer, Anticancer Res. 34 (2014) 6861–6875.

29. X. Wang, Y. Ouyang, J. Liu, M. Zhu, G. Zhao, W. Bao and F. B. Hu, Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies, Br. Med. J. 349 (2014) Article ID g4490 (14 pages);

30. K. Y. Wolin, K. Carson and G. A. Colditz, Obesity and cancer, Oncologist 15 (2010) 556–565;

31. A. P. Coll, Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential? Clin. Sci. (London) 113 (2007) 171–182;

32. C. M. Dieli-Conwright, K. Lee and J. L. Kiwata, Reducing the risk of breast cancer recurrence: An evaluation of the effects and mechanisms of diet and exercise, Curr. Breast Cancer Rep. 8 (2016) 139–150;

33. B. Yan, L. M. Yang, L. P. Hao, C. Yang, L. Quan, L. H. Wang, Z. Wu, X. P. Li, Y. T. Gao, Q. Sun and J. M. Yuan, Determinants of quality of life for breast cancer patients in Shanghai, China, PLoS ONE 11 (2016) Article ID e0153714 (14 pages);

34. M. Keimling, G. Behrens, D. Schmid, C. Jochem and M. F. Leittzmann, The association between physical activity and bladder cancer: a systematic review and meta-analysis, Br. J. Cancer 110 (2014) 1862–1870;

35. J. Gerritsen and A. Vincent, Exercise improves quality of life in patients with cancer: a systemic review and meta-analysis of randomized controlled trials, Br. J. Sport Med. 50 (2016) 796–803;

36. M. D. Holmes, W. Y. Chen, D. Feskanich, C. H. Kroenke and G. A. Colditz, Physical activity and survival after breast cancer diagnosis, J. Am. Med. Assoc. 293 (2005) 2479–2486;

37. B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts and P. Walter, Molecular Biology of the Cell, 4th ed., Garland Science, New York 2002.

38. N. Mavaddat, A. C. Antoniou, D. F. Easton and M. Garcia-Closas, Genetic susceptibility of breast cancer, Mol. Oncol. 4 (2010) 174–191;

39. P. D. Pharaoh, J. M. Lipscombe, K. L. Redman, N. E. Day, D. F. Easton and B.A. Ponder, Familial predisposition to breast cancer in a British population: implications for prevention, Eur. J. Cancer 36 (2000) 773–779;

40. U. Krug, A. Ganser and H. P. Koeffler, Tumor suppression genes in normal and malignant hematopoiesis, Oncogene 21 (2002) 3475–3495;

41. N. Mavaddat, A. M. Dunning, B. A. Ponder, D. F. Easton and P. D. Pharaoh, Common genetic variation in candidate genes and susceptibility to subtypes of breast cancer, Cancer Epidemiol. Biomarkers Prev. 18 (2009) 255–259;

42. A. Jemal, F. Bray, M. M. Center, J. Ferlay, E. Ward and D. Forman, Global cancer statistics, CA Cancer J. Clin. 61 (2011) 69–90;

43. M. Furrukh, Tobacco smoking and lung cancer, Sultan Qaboos Univ. Med. J. 13 (2013) 345–358.

44. X. Q. Jiang, X. D. Mei and D. Di Feng, Air pollution and chronic airway diseases: what should people know and do? J. Thorac. Dis. 8 (2016) E31-E40;

45. United States Environmental Protection Agency, Health Assessment Document for Diesel Engine Exhaust, USEPA Washington DC, 2002;; last access date November 30, 2017.

46. P. Farbicka and A. Nowicki, Palliative care in patients with lung cancer, Contemp. Oncol. 17 (2013) 238–245;

47. S. Ahn, S. H. Hwang, J. Han, Y. L. Choi, S. H. Lee, J. S. Ahn, K. Park, M. J. Ahn and W. Y. Park, Transformation to small cell lung cancer of pulmonary adenocarcinoma: clinicopathologic analysis of six cases, J. Pathol. Transl. Med. 50 (2016) 258–263;

48. M. G. Oser, M. J. Niederst, L. V. Sequist and J. A. Engelman, Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin, Lancet Oncol. 16 (2015) Article ID e165–172;

49. B. Gholipour, Leukemia: Types, symptoms and treatment, Live Sciences Publication, Paris;; last access November 15, 2017.

50. M. Trendowski, The inherent metastasis of leukaemia and its exploitation by sonodynamic therapy, Crit. Rev. Oncol. Hematol. 94 (2015) 149–163;

51. G. N. Waite, Blood and immunology. Chapter 9. Blood components in: Medical Physiology: Principles for Clinical Medicine, 3rd ed. (R. A. Rhoades and D. R. Bell, Eds.), Lippincott Williams and Wilkins, Baltimore 2009, pp. 169–171.

52. I. Z. Al-Mohsen, D. A. Sutton, L. Sigler, E. Almodovar, N. Mahgoub, H. Frayha, S. Al-Hajjar, M. G. Rinaldi and T. J. Walsh, Acrophialophora fusisipora brain abscess in a child with acute lymphoblastic leukemia: Review of cases and taxonomy, J. Clin. Microbiol. 38 (2000) 4569–4573.

53. R. Wakeford, M. P. Little and G. M. Kendall, Risk of childhood leukemia after low-level exposure to ionizing radiation, Expert. Rev. Hematol. 3 (2010) 251–254;

54. M. M. Jacobs, T. F. Malloy, J. A. Tickner and S. Edwards, Alternatives assessment frameworks: Research needs for the informed substitution of hazardous chemicals, Environ. Health Perspect. 124 (2016) 265–280;

55. J. B. Liao, Viruses and human cancer, Yale J. Biol. Med. 79 (2006) 115–122.

56. D. A. Pollyea, J. A. Gutman, L. Gore, C. A. Smith and C. T. Jordan, Targeting acute myeloid leukemia stem cells: A review and principles for the development of clinical trials, Haematologica 99 (2014) 1277–1284;

57. M. Riihimäki, A. Hemminki, J. Sundquist and K. Hemminki, Patterns of metastasis in colon and rectal cancer, Sci. Rep. 6 (2016) Article ID 29765;

58. M. Fleming, S. Ravula, S. F. Tatishchev and H. L. Wang, Colorectal carcinoma: Pathologic aspects, J. Gastrointest. Oncol. 3 (2012) 153–173;

59. D. M. Parkin, S. L. Whelan, J. Ferlay, L. Teppo and D. B. Thomas (Eds.), Cancer Incidence in Five Continents, IARC Scientific Publications No. 155, International Agency for Research on Cancer, Lyon 2002, Vol. VIII.

60. M. K. Mishra and K. S. Bishnupuri, Epigenetics of colorectal cancer, in: Epigenetic Advancements in Cancer, Springer International Publishing, New York 2016, pp. 98–99.

61. F. A. Haggar and R. P. Boushey, Colorectal cancer epidemiology: Incidence, mortality, survival, and risk factor, Clin. Colon Rectal Surg. 22 (2009) 191–197;

62. G. S. Cooper, F. Xu, J. S. B. Sloan, M. D. Schluchter and S. M. Koroukian, Prevalence and predictors of interval colorectal cancers in medicine beneficiaries, Cancer 118 (2012) 3044–3052;

63. P. J. T. López, J. S. Albero and J. A. Rodríguez-Montes, Primary and secondary prevention of colorectal cancer, Clin. Med. Insights Gastroenterol. 7 (2014) 33–46;

64. R. M. Jones, K. J. Devers, A. J. Kuzel and S. H. Woolf, Patient-reported barriers to colorectal cancer screening, Am. J. Prev. Med. 38 (2010) 508–516;

65. C. de Martel, D. Maucort-Boulch, M. Plummer and S. Franceschi, World-wide relative contribution of hepatitis B and C viruses in hepatocellular carcinoma, Hepatology 62 (2015) 1190–1200;

66. H. B. El-Serag, Epidemiology of viral hepatitis and hepatocellular carcinoma, Gastroenterology 142 (2012) 1264–1273;

67. B. Kucukcakan and Z. Hayrulai-Musliu, Challenging role of dietary aflatoxin B1 exposure and hepatitis B infection on risk of hepatocellular carcinoma, Open Access Maced. J. Med. Sci. 3 (2015) 363–369;

68. S. Lierena, M. T. Arias-Loste, A. Puente, J. Cabezas, J. Crespo and E. Fábrega, Binge drinking: Burden of liver disease and beyond, World J. Hepatol. 7 (2015) 2703–2715;

69. A. C. Wolff, A. L. Blackford, K. Visvanathan, H. S. Rugo, B. Moy, L. J. Goldstein, K. Stockerl-Goldstein, L. Neumayer, T. S. Langbaum, R. L. Theriault, M. E. Hughes, J. C. Weeks and J. E. Karp, Risk of marrow neoplasms after adjuvant breast cancer therapy: the national comprehensive cancer network experience, J. Clin. Oncol. 33 (2015) 340–348;

70. G. N. Sharma, R. Dave, J. Sanadya, P. Sharma and K. K. Sharma, Various types and management of breast cancer: An overview, J. Adv. Pharm. Technol. Res. 1 (2010) 109–126.

71. M. D. Abeloff, A. C. Wolff, B. L. Weber, T. Z. Zaks, V. Sacchini and B. McCormick, Cancer of the breast, in Abeloff’s Clinical Oncology, 4th ed. (M. D. Abeloff, J. O. Armitage, J. E. Niederhuber, M. B. Kastan and W. G. McKenna, Eds.), Elsevier Churchill Livingstone, Philadelphia 2008, pp. 1875–1943.

72. J. K. McLaughlin, W. J. Blot, S. S. Devesa and J. F. Fraumeni, Renal cancer, in: Cancer Epidemiology and Prevention, 2nd ed. (D. Schottenfeld and J. F. Fraumeni, Eds.), Oxford University Press, New York 1996, pp. 1142–1155.

73. R. Schmieder, C. Delles and F. Messerli, Diuretic therapy and the risk for renal cell carcinoma, J. Nephrol. 13 (2000) 343–346.

74. T. A. Martin, L. Ye, A. J. Sanders, J. Lane and W. G. Jiang, Cancer invasion and metastasis: Molecular and cellular perspective, in: Metastasis Cancer: Clinical and Biological Perspectives (Ed. R. Jandial), Landes Bioscience, Austin (TX) 2013, pp. 135–168.

75. M. Andreeff, D. W. Goodrich and A. B. Pardee, Cell proliferation, differentiation, and apoptosis, in: Holland-Frei Cancer Medicine, 6th ed. (D. W. Kufe and R. E. Pollock, Eds.), BC Decker Publisher, Hamilton 2003, pp. 21–34.

76. N. Plato, J. I. Martinsen, P. Sparén, G. Hillerdal and E. Weiderpass, Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban, Epidemiol. Health 38 (2016) e2016039 (25 pages);

77. J. W. Lim, D. Koh, J. S. G. Khim, G. V. Le and K. Takahashi, Preventive measures to eliminate asbestos-related diseases in Singapore, Safety Health Work 2 (2011) 201–209;

78. E. S. Lee and J. M. Lee, Imaging diagnosis of pancreatic cancer: A state-of-the-art review, World J. Gastroenterol. 20 (2014) 7864–7877;

79. K. Toshima, T. Ozawa, T. Kimura and S. Matsumura, The significant effect of the carbohydrate structures on the DNA photocleavage of the quinoxaline–carbohydrate hybrids, Bioorg. Med. Chem. Lett. 14 (2004) 2777–2779;

80. H. Gao, E. F. Yamasaki, K. K. Chan, L. L. Shen and R. M. Snapka, DNA sequence specificity for topoisomerase II poisoning by the quinoxaline anticancer drugs XK469 and CQS, Mol. Pharmacol. 63 (2003) 1382–1388;

81. G. Cheng, W. Sa, C. Cao, L. Guo, H. Hao, Z. Liu, X. Wang and Z. Yuan, Quinoxaline 1,4-di-N-oxides: Biological activities and mechanisms of actions, Front. Pharmacol. 7 (2016) 21 pages;

82. J. Yang, K. I. Amiri, J. R. Burke, J. A. Schmid and A. Richmond, BMS-345541 target inhibitor of kB kinase and induces apoptosis in melanoma: Involvement of nuclear factor kB and mitochondria pathways, Clin. Cancer Res. 12 (2006) 950–960;

83. F. Baffert, C. H. Régnier, A. De Pover, C. Pissot-Soldermann, G. A. Tavares, F. Blasco, J. Brueggen, P. Chène, P. Drueckes, D. Erdmann, P. Furet, M. Gerspacher, M. Lang, D. Ledieu, L. Nolan, S. Ruetz, J. Trappe, E. Vangrevelinghe, M. Wartmann, L. Wyder, F. Hofmann and T. Radimerski, Potent and selective inhibition of polycythemia by the quinoxaline JAK2 inhibitor NVP-BSK805, Mol. Cancer Ther. 9 (2010) 1945–1955;

84. O. Watanabe and H. Oikawa, Diversification of echinomycin molecular structure by way of chemo-enzymatic synthesis and heterologous expression of the engineered echinomycin biosynthetic pathway, Curr. Opin. Chem. Biol. 13 (2009) 189–196;

85. R. M. Rajukar, V. A. Agrawal, S. S. Thonte and R. G. Ingale, Heterocyclic chemistry of quinoxaline and potential activities of quinoxaline derivatives – A review, Pharmacophore 1 (2010) 65–76.

86. M. M. Heravi, K. Bakhtiari, M. H. Tehrami, N. M. Javadi and H. A. Oskooie, Facile synthesis of quinoxaline derivatives using o-iodoxybenzoic acid (IBX) at room temperature, Arkivoc 26 (2006) 16–22.

87. O. O. Ajani, Present status of quinoxaline motifs: Excellent pathfinders in therapeutic medicine, Eur. J. Med. Chem. 85 (2014) 688–715;

88. O. O. Ajani, C. A. Obafemi, C. O. Ikpo, K. O. Ajanaku, K. O. Ogunniran and O. O. James, Comparative study of microwave assisted and conventional synthesis of novel 2-quinoxalinone-3-hydrazone derivatives and its spectroscopic properties, Int. J. Phys. Sci. 4 (2009a) 156–164.

89. O. O. Ajani, C. A. Obafemi, C. O. Ikpo, K. O. Ogunniran and O. C. Nwinyi, Synthesis and antibacterial activity of some pyrazol-1-ylquinoxalin-2(1H)-one derivatives, Chem. Heterocycl. Comp. 45 (2009b) 1370–1378;

90. S. Sajjadifar, H. Noorizadeh, H. Veisi, O. Louie, M. Avval and M. Rezayati, A facile and efficient method for the synthesis of quinoxaline derivatives using [(sulfooxy) ethyl]sulfamic acid as a novel difunctional bronsted acid, recyclable and organocatalyst, Res. J. Pharm. Biol. Chem. Sci. 4 (2013) 906–916.

91. S. B. Lee, Y. I. Park, M. S. Dong and Y. D. Gong, Identification of 2,3,6-trisubstituted quinoxaline derivatives as a Wnt2/b-catenin pathway inhibitor in non-small-cell lung cancer cell lines, Bioorg. Med. Chem. Lett. 20 (2010a) 5900–5904;

92. S. S. Karki, R. Hazare, S. Kumar, V. S. Bhadauria, J. Balzarini and E. De Clercq, Synthesis, anticancer and cytostatic activity of some 6H-indolo [2,3-b] quinoxalines, Acta Pharm. 59 (2009) 431–440;

93. Y. B. Lee, Y. D. Gong, H. Yoon, C. H. Ahn, M. K. Jeon and J. Y. Kong, Synthesis and anticancer activity of new 1-[(5- or 6-substituted 2-alkoxyquinoxalin-3-yl)aminocarbonyl]-4-(hetero)aryl piperazine derivatives, Bioorg. Med. Chem, 18 (2010b) 7966–7974;

94. B. Zarranz, A. Jaso, I. Aldana and A. Monge, Synthesis and anticancer activity evaluation of new 2-alkylcarbonyl and 2-benzoyl-3-trifluoromethyl-quinoxaline 1,4-di-N-oxide derivative, Bioorg. Med. Chem. 12 (2004) 3711–3721;

95. S. Piras, M. Loriga, A. Carta, G. Paglietti, M. P. Costi and S. Ferrari, Novel 3-benzoyl-2-piperazinylquinoxaline derivatives as potential antitumor agents, J. Heterocycl. Chem. 43 (2006) 541–548;

96. S. T. Hazeldine, L. Polin, J. Kushner, K. White, T. H. Corbett and J. P. Horwitz, Synthetic modification of the 2-oxypropionic acid moiety in 2-{4-[(7-chloro-2-quinoxalinyl)oxy] phenoxy}propionic acid (XK469), and consequent antitumor effects. Part 4, Bioorg. Med. Chem. 13 (2005) 3910–3920;

97. F. Grande, F. Aiello, O. De Grazia, A. Brizzi, A. Garofalo and N. Neamati, Synthesis and antitumor activities of a series of novel quinoxalinhydrazides, Bioorg. Med. Chem. 15 (2007) 288–294;

98. G. Moarbess, C. Deleuze-Masquefa, V. Bonnard, S. Gayraud-Paniagua, J. Vidal, F. Bressolle, F. Pinguet and B. Pierre-Antoine, In vitro and in vivo anti-tumoral activities of imidazo[1,2-a]quinoxaline, imidazo[1,5-a]quinoxaline, and pyrazolo[1,5-a]quinoxaline derivatives, Bioorg. Med. Chem. 16 (2008) 6601–6610;

99. S. Tanimori, T. Nishimura and M. Kirihata, Synthesis of novel quinoxaline derivatives and its cytotoxic activities, Bioorg Med Chem Lett. 19 (2009) 4119–4121;

100. P. J. Kaboli, A. Rahmat, P. Ismail and K. H. Ling, Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer, Eur. J. Pharmacol. 740 (2014) 584–595;

101. U. Das, H. N. Pati, A. K. Panda, E. De Clercq and J. Balzarini, J. Molnár, Z. Baráth, I. Ocsovszki, M. Kawase, L. Zhou, H. Sakagami and J. R. Dimmock, 2-(3-Aryl-2-propenoyl)-3-methyl quinoxaline-1,4-dioxides: A novel cluster of tumor-specific cytotoxins which reverse multidrug resistance, Bioorg. Med. Chem. 17 (2009) 3909–3915;

102. K. Ghattass, S. El-Sitt, K. Zibara, S. Rayes, M. Haddadin, M. El-Sabban and H. Gali-Muhtasib, The quinoxaline di-N-oxide DCQ blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway, Mol. Cancer 13 (2014) 12–25;

103. S. A. Galal, A. S. Abdelsamie, H. Tokuda, N. Suzuki, A. Lida, M. M. Elhefnawi, R. A. Ramadan, M. H. E. Atta and H. I. El Diwani, Part I: Synthesis, cancer chemopreventive activity and molecular docking study of novel quinoxaline derivatives, Eur. J. Med. Chem. 46 (2011) 327–340;

104. M. M. Ghorab, F. A. Ragab, H. I. Heiba, M. G. El-Ghazzar and M. G. El-Ghazzar, Synthesis, in-vitro anticancer screening and radiosensitizing evaluation of some new N-(quinoxalin-2-yl) benzene sulfonamide derivatives, Arzneimittelforschung 62 (2012) 46–52;

105. Y. Hu, Q. Xia, S. Shangguan, X. Liu, Y. Hu and R. Sheng, Synthesis and biological evaluation of 3-aryl-quinoxaline-2-carbonitrile 1,4-di-N-oxide derivatives as hypoxic selective anti-tumor agents, Molecules 17 (2012) 9683–9696;

106. B. Solano, V. Junnotula, A. Marin, R. Villar, A. Burguete, E. Vicente, S. Perez-Silanes, I. Aldana, A. Monge, S. Dutta, U. Sarkar and K. S. Gates, Synthesis and biological evaluation of new 2-arylcarbonyl-3-trifluoromethylquinoxaline 1,4-di-N-oxide derivatives and their reduced analogues, J. Med. Chem. 50 (2007) 5485–5492;

107. B. Zarranz, A. Jaso, I. Aldana and A. Monge, Synthesis and anticancer activity evaluation of new 2-alkylcarbonyl and 2-benzoyl-3-trifluoromethyl-quinoxaline 1,4-di-N-oxide derivatives. Bioorg. Med. Chem. 12 (2004) 3711–3721;

108. J. Jampilek, Recent advances in design of potential quinoxaline anti-infectives, Curr. Med. Chem. 21 (2014) 4347–4373;

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