Fused pyrrolo-pyridines and pyrrolo-(iso)quinoline as anticancer agents

References

1. World Health Organization Cancer Programme. Available from: http://www.who.int/cancer/en/.Search in Google Scholar

2. Zhong, L, Li, YS, Xiong, L, Wang, WJ, Wu, M, Yuan, T, et al.. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther 2021;6:201. https://doi.org/10.1038/s41392-021-00572-w.Search in Google Scholar PubMed PubMed Central

3. Zhao, Y, Mu, X, Du, G. Microtubule-stabilizing agents: new drug discovery and cancer therapy. Pharmacol Ther 2016;162:134–43. https://doi.org/10.1016/j.pharmthera.2015.12.006.Search in Google Scholar PubMed

4. Prasad, S, Gupta, SC, Aggarwal, BB. Serendipity in cancer drug discovery: rational or coincidence? Trends Pharmacol Sci 2016;37:435–50. https://doi.org/10.1016/j.tips.2016.03.004.Search in Google Scholar PubMed

5. Berube, G. An overview of molecular hybrids in drug discovery. Expet Opin Drug Discov 2016;11:281–305. https://doi.org/10.1517/17460441.2016.1135125.Search in Google Scholar PubMed

6. Trendowski, M. Recent advances in the development of antineoplastic agents derived from natural products. Drugs 2015;75:1993–2016. https://doi.org/10.1007/s40265-015-0489-4.Search in Google Scholar PubMed PubMed Central

7. Cheng, B, Yuan, WE, Su, J, Liu, Y, Chen, J. Recent advances in small molecule based cancer immunotherapy. Eur J Med Chem 2018;157:582–97. https://doi.org/10.1016/j.ejmech.2018.08.028.Search in Google Scholar PubMed

8. Vitaku, E, Smith, DT, Njardarson, JT. Analysis of the structural diversity, substitution patterns, and frequency of nitrogen heterocycles among U.S. FDA approved pharmaceuticals. J Med Chem 2014;57:10257–74. https://doi.org/10.1021/jm501100b.Search in Google Scholar PubMed

9. Sharma, V, Gupta, M, Kumar, P, Sharma, A. Comprehensive review on fused heterocyclic as DNA intercalators: promising anticancer agents. Curr Pharmaceut Des 2021;27:15–42. https://doi.org/10.2174/1381612826666201118113311.Search in Google Scholar PubMed

10. Ahmad, S, Alam, O, Naim, MJ, Shaquiquzzaman, M, Alam, MM, Iqbal, M. Pyrrole: an insight into recent pharmacological advances with structure activity relationship. Eur J Med Chem 2018;157:527–61. https://doi.org/10.1016/j.ejmech.2018.08.002.Search in Google Scholar PubMed

11. Gholap, SS. Pyrrole: an emerging scaffold for construction of valuable therapeutic agents. Eur J Med Chem 2016;110:13–31. https://doi.org/10.1016/j.ejmech.2015.12.017.Search in Google Scholar PubMed

12. Prachayasittikul, S, Pingaew, R, Worachartcheewan, A, Sinthupoom, N, Prachayasittikul, V, Ruchirawat, S, et al.. Roles of pyridine and pyrimidine derivatives as privileged scaffolds in anticancer agents. Mini Rev Med Chem 2017;17:869–901. https://doi.org/10.2174/1389557516666160923125801.Search in Google Scholar PubMed

13. Chaubey, A, Pandeva, SN. Pyridine - a versatile nucleus in pharmaceutical field. Asian J Pharmaceut Clin Res 2011;4:5–8.Search in Google Scholar

14. Chiacchio, MA, Iannazzo, D, Romeo, R, Giofre, SV, Legnani, L. Pyridine and pyrimidine derivatives as privileged scaffolds in biologically active agents. Curr Med Chem 2019;26:7166–95. https://doi.org/10.2174/0929867325666180904125400.Search in Google Scholar PubMed

15. Singh, GS, Mmatli, E. Recent progress in synthesis and bioactivity studies of indolizines. Eur J Med Chem 2011;46:5237–57. https://doi.org/10.1016/j.ejmech.2011.08.042.Search in Google Scholar PubMed

16. Sharma, V, Kumar, V. Indolizine: a biologically active moiety. Med Chem Res 2014;23:3593–606. https://doi.org/10.1007/s00044-014-0940-1.Search in Google Scholar

17. Sandeep, C, Venugopala, KN, Khedr, MA, Attimarad, M, Padmashali, B, Kulkarni, RS, et al.. Review on chemistry of natural and synthetic indolizines with their chemical and pharmacological properties. J Basic Clin Pharm 2017;8:49–60.Search in Google Scholar

18. Dawood, KM, Abbas, AA. Inhibitory activities of indolizine derivatives: a patent review. Expert Opin Ther Pat 2020;30:695–714. https://doi.org/10.1080/13543776.2020.1798402.Search in Google Scholar PubMed

19. Vemula, VR, Vurukonda, S, Bairi, CK. Indolizine derivatives: recent advances and potential pharmacological activities. Int J Pharmaceut Sci Rev Res 2011;11:159–63.Search in Google Scholar

20. Ghinea, IO, Dinica, RM. Breakthroughs in indole and indolizine chemistry – new synthetic pathways, new applications. In: Varala, R, editor. Scope of selective heterocycles from organic and pharmaceutical perspective. London, UK: IntechOpen Book Series; 2017.10.5772/62079Search in Google Scholar

21. Jin, S, Wang, L, Han, H, Liu, X, Bu, Z, Wang, Q. Assembly of functionalized π-extended indolizine polycycles through dearomative [3 + 2] cycloaddition/oxidative decarbonylation. Chem Commun (J Chem Soc Sect D) 2021;57:359–62. https://doi.org/10.1039/d0cc07116a.Search in Google Scholar PubMed

22. Su, K, Guo, X, Liu, Y, Lu, Y, Chen, B. Indolizine synthesis via radical cyclization and demethylation of sulfoxonium ylides and 2-(pyridin-2-yl)acetate derivatives. Org Chem Front 2021;8:4177–82. https://doi.org/10.1039/d1qo00550b.Search in Google Scholar

23. Kim, ND, Park, ES, Kim, YH, Moon, SK, Lee, SS, Ahn, SK, et al.. Structure-based virtual screening of novel tubulin inhibitors and their characterization as anti-mitotic agents. Bioorg Med Chem 2010;18:7092–100. https://doi.org/10.1016/j.bmc.2010.07.072.Search in Google Scholar PubMed

24. Abuhaie, CM, Bicu, E, Rigo, B, Gautret, P, Belei, D, Farce, A, et al.. Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents. Bioorg Med Chem Lett 2013;23:147–52. https://doi.org/10.1016/j.bmcl.2012.10.135.Search in Google Scholar PubMed

25. Ghinet, A, Abuhaie, CM, Gautret, P, Rigo, B, Dubois, J, Farce, A, et al.. Studies on indolizines. Evaluation of their biological properties as microtubule-interacting agents and as melanoma targeting compounds. Eur J Med Chem 2015;89:115–27. https://doi.org/10.1016/j.ejmech.2014.10.041.Search in Google Scholar PubMed

26. Lucescu, L, Ghinet, A, Belei, D, Rigo, B, Dubois, J, Bicu, E. Discovery of indolizines containing triazine moiety as new leads for the development of antitumoral agents targeting mitotic events. Bioorg Med Chem Lett 2015;25:3975–9. https://doi.org/10.1016/j.bmcl.2015.07.025.Search in Google Scholar PubMed

27. Sardaru, MC, Craciun, AM, Al Matarneh, CM, Sandu, IA, Amarandi, RM, Popovici, L, et al.. Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors. J Enzym Inhib Med Chem 2020;35:1581–95. https://doi.org/10.1080/14756366.2020.1801671.Search in Google Scholar PubMed PubMed Central

28. Dumontet, C, Jordan, MA. Microtubule-binding agents: a dynamic field of cancer therapeutics. Nat Rev Drug Discov 2010;9:790–803. https://doi.org/10.1038/nrd3253.Search in Google Scholar PubMed PubMed Central

29. Le Broc-Ryckewaert, D, Pommery, N, Pommery, J, Ghinet, A, Farce, A, Wiart, JF, et al.. In vitro metabolism of Phenstatin: potential pharmacological consequences. Drug Metabol Lett 2011;5:209–15. https://doi.org/10.2174/187231211796904973.Search in Google Scholar PubMed

30. Shen, YM, Lv, PC, Chen, W, Liu, PG, Zhang, MZ, Zhu, HL. Synthesis and antiproliferative activity of indolizine derivatives incorporating a cyclopropylcarbonyl group against Hep-G2 cancer cell line. Eur J Med Chem 2010;45:3184–90. https://doi.org/10.1016/j.ejmech.2010.02.056.Search in Google Scholar PubMed

31. Moon, SH, Jung, Y, Kim, SH, Kim, I. Synthesis, characterization and biological evaluation of anti-cancer indolizine derivatives via inhibiting β-catenin activity and activating p53. Bioorg Med Chem Lett 2016;26:110–3. https://doi.org/10.1016/j.bmcl.2015.11.021.Search in Google Scholar PubMed

32. Sandeep, C, Padmashali, B, Venugopala, KN, Kulkarni, RS, Venugopala, R, Odhav, B. Synthesis and characterization of ethyl 7-acetyl-2-substituted 3-(substituted benzoyl)indolizine-1-carboxylates for in vitro anticancer activity. Asian J Chem 2016;28:1043–8. https://doi.org/10.14233/ajchem.2016.19582.Search in Google Scholar

33. Park, S, Kim, EH, Kim, J, Kim, SH, Kim, I. Biological evaluation of indolizine-chalcone hybrids as new anticancer agents. Eur J Med Chem 2018;144:435–43. https://doi.org/10.1016/j.ejmech.2017.12.056.Search in Google Scholar PubMed

34. Liu, Y, Shao, E, Zhang, Z, Yang, D, Li, G, Cao, H, et al.. A novel indolizine derivative induces apoptosis through the mitochondria p53 pathway in HepG2 cells. Front Pharmacol 2019;10:762. https://doi.org/10.3389/fphar.2019.00762.Search in Google Scholar PubMed PubMed Central

35. Mahanthesha, G, Suresh, T, Yadav, BD. Synthesis and characterization of (3-chlorophenyl) (1-(5-phenyl-1,3,4-oxadiazol-2-yl)indolizin-3-yl)methanone derivatives as anticancer and antimicrobial agents. Chem Data Coll 2021;33:100691.10.1016/j.cdc.2021.100691Search in Google Scholar

36. Han, Y, Dong, W, Guo, Q, Li, X, Huang, L. The importance of indole and azaindole scaffold in the development of antitumor agents. Eur J Med Chem 2020;203:112506. https://doi.org/10.1016/j.ejmech.2020.112506.Search in Google Scholar PubMed

37. Popowycz, F, Routier, S, Joseph, B, Merour, JY. Synthesis and reactivity of 7-azaindole (1H-pyrrolo[2,3-b]pyridineH-pyrrolo[2,3-b). Tetrahedron 2007;63:1031–64. https://doi.org/10.1016/j.tet.2006.09.067.Search in Google Scholar

38. Motati, DR, Amaradhi, R, Ganesh, T. Recent developments in the synthesis of azaindoles from pyridine and pyrrole building blocks. Org Chem Front 2021;8:466–513. https://doi.org/10.1039/d0qo01079k.Search in Google Scholar

39. Mérour, JY, Routier, S, Suzenet, F, Joseph, B. Recent advances in the synthesis and properties of 4-, 5-, 6- or 7-azaindoles. Tetrahedron 2013;69:4767–834. https://doi.org/10.1016/j.tet.2013.03.081.Search in Google Scholar

40. Chapman, PB, Hauschild, A, Robert, C, Haanen, JB, Ascierto, P, Larkin, J, et al.. Improved survival with vemurafenib in Melanoma with BRAF V600E mutation. N Engl J Med 2011;364:2507–16. https://doi.org/10.1056/nejmoa1103782.Search in Google Scholar

41. Tap, WD, Gelderblom, H, Palmerini, E, Desai, J, Bauer, S, Blay, JY, et al.. Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial. Lancet 2019;394:478–87. https://doi.org/10.1016/s0140-6736(19)30764-0.Search in Google Scholar

42. Diana, P, Carbone, A, Barraja, P, Montalbano, A, Parrino, B, Lopergolo, A, et al.. Synthesis and antitumor activity of 3-(2-phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles. ChemMedChem 2011;6:1300–9. https://doi.org/10.1002/cmdc.201100078.Search in Google Scholar PubMed

43. Aly, HM, El-Gazzar, MG. Novel pyrazole derivatives as anticancer and radiosensitizing agents. Arzneimittelforschung 2012;62:105–12. https://doi.org/10.1055/s-0031-1297252.Search in Google Scholar PubMed

44. Zhang, P, Sui, D, Sun, W, Yu, X, Qu, S, Hu, J, et al.. Synthesis and antitumor activity of a new 7-azaindole derivative. Chem Res Chin Univ 2014;30:420–4. https://doi.org/10.1007/s40242-014-3468-5.Search in Google Scholar

45. Lee, HY, Tsai, AC, Chen, MC, Shen, PJ, Cheng, YC, Kuo, CC, et al.. Azaindolylsulfonamides, with a more selective inhibitory effect on histone deacetylase 6 activity, exhibit antitumor activity in colorectal cancer HCT116 cells. J Med Chem 2014;57:4009–22. https://doi.org/10.1021/jm401899x.Search in Google Scholar PubMed

46. Cincinelli, R, Musso, L, Merlini, L, Giannini, G, Vesci, L, Milazzo, FM, et al.. 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorg Med Chem 2014;22:1089–103. https://doi.org/10.1016/j.bmc.2013.12.031.Search in Google Scholar PubMed

47. Cheng, X, Merz, KH, Vatter, S, Christ, J, Wölfl, S, Eisenbrand, G. 7,7′-Diazaindirubin-a small molecule inhibitor of casein kinase 2 in vitro and in cells. Bioorg Med Chem 2014;22:247–55. https://doi.org/10.1016/j.bmc.2013.11.031.Search in Google Scholar PubMed

48. Štarha, P, Trávníček, Z, Popa, I, Dvořák, Z. Synthesis, characterization and in vitro antitumor activity of Platinum (II) oxalato complexes involving 7-azaindole derivatives as coligands. Molecules 2014;19:10832–44.10.3390/molecules190810832Search in Google Scholar PubMed PubMed Central

49. Štarha, P, Dvořák, Z, Trávníček, Z. Highly and broad-spectrum in vitro antitumor active cis-dichloridoplatinum(II) complexes with 7-azaindoles. PLoS One 2015;10:e0136338.10.1371/journal.pone.0136338Search in Google Scholar PubMed PubMed Central

50. Štarha, P, Trávníček, Z, Drahos, B, Dvořák, Z. In vitro antitumor active Gold (I) triphenylphosphane complexes containing 7-azaindoles. Int J Mol Sci 2016;17:2084.10.3390/ijms17122084Search in Google Scholar PubMed PubMed Central

51. Zhu, W, Wang, W, Xu, S, Tang, Q, Luo, R, Wang, M, et al.. Design, synthesis, and docking studies of phenylpicolinamide derivatives bearing 1H-pyrrolo[2,3-b]pyridineH-pyrrolo[2,3-b moiety as c-Met inhibitorsc-. Bioorg Med Chem 2016;24:812–9. https://doi.org/10.1016/j.bmc.2016.01.001.Search in Google Scholar PubMed

52. Zhu, W, Wang, W, Xu, S, Wang, J, Tang, Q, Wu, C, et al.. Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridineH-pyrrolo[2,3-b moiety as c-Met inhibitorsc-. Bioorg Med Chem 2016;24:1749–56. https://doi.org/10.1016/j.bmc.2016.02.046.Search in Google Scholar PubMed

53. Spanò, V, Attanzio, A, Cascioferro, S, Carbone, A, Montalbano, A, Barraja, P, et al.. Synthesis and antitumor activity of new thiazole nortopsentin analogs. Mar Drugs 2016;14:226. https://doi.org/10.3390/md14120226.Search in Google Scholar PubMed PubMed Central

54. Carbone, A, Pennati, M, Parrino, B, Lopergolo, A, Barraja, P, Montalbano, A, et al.. Novel 1H-pyrrolo[2,3-b]pyridineH-pyrrolo[2,3-b derivatives nortopsentin analogues: synthesis and antitumor activity in peritoneal mesothelioma experimental models. J Med Chem 2013;56:7060–72. https://doi.org/10.1021/jm400842x.Search in Google Scholar PubMed

55. Tang, Q, Wang, L, Duan, Y, Wang, W, Huang, S, Zhi, J, et al.. Discovery of novel 7-azaindole derivatives bearing dihydropyridazine moiety as c-Met kinasec- inhibitors. Eur J Med Chem 2017;133:97–106. https://doi.org/10.1016/j.ejmech.2017.03.045.Search in Google Scholar PubMed

56. Yuan, Z, Sun, Q, Li, D, Miao, S, Chen, S, Song, L, et al.. Design, synthesis and anticancer potential of NSC-319745 hydroxamic acid derivatives as DNMT and HDAC inhibitors. Eur J Med Chem 2017;134:281–92. https://doi.org/10.1016/j.ejmech.2017.04.017.Search in Google Scholar PubMed

57. Parrino, B, Attanzio, A, Spano, V, Cascioferro, S, Montalbano, A, Barraja, P, et al.. Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues. Eur J Med Chem 2017;138:371–83. https://doi.org/10.1016/j.ejmech.2017.06.052.Search in Google Scholar PubMed

58. Hulpia, F, Noppen, S, Schols, D, Andrei, G, Snoeck, R, Liekens, S, et al.. Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: discovery of C7-deazapurine analogs as potent antiproliferative nucleosides. Eur J Med Chem 2018;157:248–67. https://doi.org/10.1016/j.ejmech.2018.07.062.Search in Google Scholar PubMed PubMed Central

59. Wang, W, Xu, S, Duan, Y, Liu, X, Li, X, Wang, C, et al.. Synthesis and bioevaluation and docking study of 1H-pyrrolo[2,3-b]pyridine H-pyrrolo[2,3-b derivatives bearing aromatic hydrazone moiety as c-Met inhibitorsc-. Eur J Med Chem 2018;145:315–27. https://doi.org/10.1016/j.ejmech.2017.12.078.Search in Google Scholar PubMed

60. Wang, LX, Liu, X, Xu, S, Tang, Q, Duan, Y, Xiao, Z, et al.. Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinasec- inhibitors. Eur J Med Chem 2017;141:538–51. https://doi.org/10.1016/j.ejmech.2017.10.027.Search in Google Scholar PubMed

61. Liua, H, Duan, Y, Xiong, H, Zhang, J, Huang, S, Chen, T, et al.. Discovery of novel pyrrolo[2,3-b]pyridine derivatives bearing 4-oxoquinoline moiety as potential antitumor inhibitor. Bioorg Med Chem Lett 2020;30:126848. https://doi.org/10.1016/j.bmcl.2019.126848.Search in Google Scholar PubMed

62. Cascioferro, S, Attanzio, A, Di Sarno, V, Musella, S, Tesoriere, L, Cirrincione, G, et al.. New 1,2,4-oxadiazole nortopsentin derivatives with cytotoxic activity. Mar Drugs 2019;17:35. https://doi.org/10.3390/md17010035.Search in Google Scholar PubMed PubMed Central

63. Dongare, SB, Bandgar, BP, Bhale, PS, Shringare, SN, Chavan, HV. Design, synthesis, and spectroscopic study of 7-azaindolyl hydrazones with anti-breast cancer activity. Croat Chem Acta 2019;92:1–9. https://doi.org/10.5562/cca3418.Search in Google Scholar

64. Diao, PC, Hu, MJ, Yang, HK, You, WW, Zhao, PL. Facile one-pot synthesis, antiproliferative evaluation and structure-activity relationships of 3-amino-1H-indoles and 3-amino-1H-7-azaindoles. Bioorg Chem 2019;88:102914. https://doi.org/10.1016/j.bioorg.2019.04.008.Search in Google Scholar PubMed

65. Lee, SH, Kim, K, Jeon, YU, Kundu, A, Dey, P, Hwang, JY, et al.. Lewis acid-mediated cross-coupling reaction of 7-azaindoles and aldehydes: cytotoxic evaluation of C3-linked bis-7-azaindoles. Tetrahedron Lett 2019;60:150974. https://doi.org/10.1016/j.tetlet.2019.150974.Search in Google Scholar

66. Ganser, C, Lauermann, E, Maderer, A, Stauder, T, Kramb, JP, Plutizki, S, et al.. Novel 3-azaindolyl-4-arylmaleimides exhibiting potent antiangiogenic efficacy, protein kinase inhibition, and antiproliferative activity. J Med Chem 2012;55:9531–40. https://doi.org/10.1021/jm301217c.Search in Google Scholar PubMed

67. Lee, HY, Pan, SL, Su, MC, Liu, YM, Kuo, CC, Chang, YT, et al.. Furanyl-azaindoles: potent anticancer agents in vitro and in vivo. J Med Chem 2013;56:8008–18. https://doi.org/10.1021/jm4011115.Search in Google Scholar PubMed

68. Bartoli, G, Palmieri, G, Bosco, M, Dalpozzo, R. The reaction of vinyl Grignard reagents with 2-substituted nitroarenes: a new approach to the synthesis of 7-substituted indoles. Tetrahedron Lett 1989;30:2129–32. https://doi.org/10.1016/s0040-4039(01)93730-x.Search in Google Scholar

69. Liu, Y, Peng, X, Guan, X, Lu, D, Xi, Y, Jin, S, et al.. Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors. Eur J Med Chem 2017;126:122–32. https://doi.org/10.1016/j.ejmech.2016.10.003.Search in Google Scholar PubMed

70. Zhang, J, Chen, P, Zhu, P, Zheng, P, Wang, T, Wang, L, et al.. Development of small-molecule BRD4 degraders based on pyrrolopyridone derivative. Bioorg Chem 2020;99:103817. https://doi.org/10.1016/j.bioorg.2020.103817.Search in Google Scholar PubMed

71. Kim, HJ, Jung, MH, Kim, H, El-Gamal, MI, Sim, TB, Lee, SH, et al.. Synthesis and antiproliferative activity of pyrrolo[3,2-b]pyridine-bderivatives against melanoma. Bioorg Med Chem Lett 2010;20:413–7. https://doi.org/10.1016/j.bmcl.2009.08.005.Search in Google Scholar PubMed

72. Zhang, Y, Zhao, Y, Tebben, AJ, Sheriff, S, Ruzanov, M, Fereshteh, MP, et al.. Discovery of 4-azaindole inhibitors of TGFβRI as immuno-oncology agents. ACS Med Chem Lett 2018;9:1117–22. https://doi.org/10.1021/acsmedchemlett.8b00357.Search in Google Scholar PubMed PubMed Central

73. Štarha, P, Vanco, J, Trávníček, Z, Hosek, J, Klusakova, J, Dvořák, Z. Platinum(II) iodido complexes of 7-azaindoles with significant antiproliferative effects: an old story revisited with unexpected outcomes. PLoS One 2016;11:e0165062.10.1371/journal.pone.0165062Search in Google Scholar PubMed PubMed Central

74. Štarha, P, Trávníček, Z, Vanco, J, Dvořák, Z. In vitro anticancer active cis-Pt (II)-diiodido complexes containing 4-azaindoles. J Biol Inorg Chem 2019;24:257–69.10.1007/s00775-019-01643-8Search in Google Scholar PubMed

75. Swamy, PV, Kumar, VK, Raju, RR, Reddy, RV, Chatterjee, A, Kiran, G, et al.. Amide derivatives of 4-azaindole: design, synthesis, and EGFR targeting anticancer agents. Synth Commun 2020;50:71–84. https://doi.org/10.1080/00397911.2019.1683206.Search in Google Scholar

76. El-Gamal, MI, Jung, MH, Oh, CH. Discovery of a new potent bisamide FMS kinase inhibitor. Bioorg Med Chem Lett 2010;20:3216–8. https://doi.org/10.1016/j.bmcl.2010.04.088.Search in Google Scholar PubMed

77. Yun, HJ, Kim, G, Khanal, P, Kim, K, Oh, CH, Choi, HK, et al.. Inhibitory effects of a new 1H-pyrrolo[3,2-c]pyridine-c derivative, KIST101029, on activator protein-1 activity and neoplastic cell transformation induced by insulin like growth factor-1. Biol Pharm Bull 2013;36:1466–73. https://doi.org/10.1248/bpb.b13-00244.Search in Google Scholar PubMed

78. El-Gamal, MI, Jung, MH, Lee, WS, Sim, T, Yoo, KH. Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine-c derivatives against melanoma cell lines. Eur J Med Chem 2011;46:3218–26. https://doi.org/10.1016/j.ejmech.2011.04.031.Search in Google Scholar PubMed

79. Jung, MH, El-Gamal, MI, Abdel-Maksoud, MS, Sim, T, Yoo, KH, Oh, CH. Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine-c derivatives against melanoma cell lines. Part 2. Bioorg Med Chem Lett 2012;22:4362–7. https://doi.org/10.1016/j.bmcl.2012.05.004.Search in Google Scholar PubMed

80. El-Gamal, MI, Oh, CH. Pyrrolo[3,2-c]pyridine derivatives with potential inhibitory effect against FMS kinase: in vitro biological studies. J Enzym Inhib Med Chem 2018;33:1160–6. https://doi.org/10.1080/14756366.2018.1491563.Search in Google Scholar PubMed PubMed Central

81. Nguyen, CH, Bisagni, E, Lhoste, JM. Synthèse des dérivés N-5 substitués des 5H-pyrido [4,3-b]benzo[f]indoles, isomères des 6H-pyrido[4,3-b] carbazoles (ellipticines). Can J Chem 1986;64:454–551. https://doi.org/10.1139/v86-087.Search in Google Scholar

82. Prudent, R, Vassal-Stermann, E, Nguyen, CH, Mollaret, M, Viallet, J, Desroches-Castan, A, et al.. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities. Br J Pharmacol 2013;168:673–85. https://doi.org/10.1111/j.1476-5381.2012.02230.x.Search in Google Scholar PubMed PubMed Central

83. Liu, TC, Peng, X, Ma, YC, Ji, YC, Chen, DQ, Zheng, MY, et al.. Discovery of a new series of imidazo[1,2-a]pyridine compounds as selective c-Met inhibitorsc-Met . Acta Pharmacol Sin 2016;37:698–707. https://doi.org/10.1038/aps.2016.11.Search in Google Scholar PubMed PubMed Central

84. Organ, SL, Tsao, MS. An overview of the c-MET signaling pathway. Ther Adv Med Oncol 2011;3:S7–19. https://doi.org/10.1177/1758834011422556.Search in Google Scholar PubMed PubMed Central

85. Dong, G, Chen, W, Wang, X, Yang, X, Xu, T, Wang, P, et al.. Small molecule inhibitors simultaneously targeting cancer metabolism and epigenetics: discovery of novel nicotinamide phosphoribosyltransferase (NAMPT) and histone deacetylase (HDAC) dual inhibitors. J Med Chem 2017;60:7965–83. https://doi.org/10.1021/acs.jmedchem.7b00467.Search in Google Scholar PubMed

86. Wojcicka, A, Redzicka, A. An overview of the biological activity of pyrrolo[3,4-c]pyridine-c derivatives. Pharmaceuticals 2021;14:354. https://doi.org/10.3390/ph14040354.Search in Google Scholar PubMed PubMed Central

87. Kalai, T, Kuppusamy, ML, Balog, M, Selvendiran, K, Rivera, BK, Kuppusamy, P, et al.. Synthesis of N-substituted 3,5-bis(arylidene)-4-piperidones with high antitumor and antioxidant activity. J Med Chem 2011;54:5414–21. https://doi.org/10.1021/jm200353f.Search in Google Scholar PubMed

88. Dragovich, PS, Bair, KW, Baumeister, T, Ho, YC, Liederer, BM, Liu, X, et al.. Identification of 2,3-dihydro-1H-pyrrolo[3,4-c]pyridine-derived ureas as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT). Bioorg Med Chem Lett 2013;23:4875–85. https://doi.org/10.1016/j.bmcl.2013.06.090.Search in Google Scholar PubMed

89. Lam, B, Arikawa, Y, Cramlett, J, Dong, Q, de Jong, R, Feher, V, et al.. Discovery of TAK-659 an orally available investigational inhibitor of spleen tyrosine kinase (SYK). Bioorg Med Chem Lett 2016;26:5947–50. https://doi.org/10.1016/j.bmcl.2016.10.087.Search in Google Scholar PubMed

90. Wojcicka, A, Becan, L, Junka, A, Brtoszewicz, M, Secewicz, A, Trynda, J, et al.. Synthesis and biological activity of novel 6-phenyl-1H-pyrrolo[3,4-c]pyridine-c-1,3-dione derivatives. Acta Pol Pharm Drug Res 2017;74:435–43.Search in Google Scholar

91. Mao, Y, Soni, K, Sangani, C, Yao, Y. An overview of privileged scaffold: quinolines and isoquinolines in medicinal chemistry as anticancer agents. Curr Top Med Chem 2020;20:2599–633. https://doi.org/10.2174/1568026620999200917154225.Search in Google Scholar PubMed

92. Musiol, R. An overview of quinoline as a privileged scaffold in cancer drug discovery. Expet Opin Drug Discov 2017;12:583–97. https://doi.org/10.1080/17460441.2017.1319357.Search in Google Scholar PubMed

93. Tokuyama, T, Uenoyama, K, Brown, G, Daly, JW, Witkop, B. Allenic and acetylenic spiropiperidine Alkaloids from the neotropical frog, Dendrobates histrionicus. Helv Chim Acta 1974;57:2597–604. https://doi.org/10.1002/hlca.19740570835.Search in Google Scholar PubMed

94. Dumitrascu, F, Georgescu, F, Georgescu, E, Caira, MR. Pyrroloquinolines, imidazoquinolines, and pyrroloquinazolines with a bridgehead nitrogen. Adv Heterocycl Chem 2019;129:155–244. https://doi.org/10.1016/bs.aihch.2019.01.004.Search in Google Scholar

95. Kemnitzer, W, Kuemmerle, J, Jiang, S, Zhang, HZ, Sirisoma, N, Kasibhatla, S, et al.. Discovery of 1-benzoyl-3-cyanopyrrolo[1,2-a]quinolines as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. Part 1: structure–activity relationships of the 1- and 3-positions. Bioorg Med Chem Lett 2008;18:6259–64. https://doi.org/10.1016/j.bmcl.2008.09.110.Search in Google Scholar PubMed

96. Kemnitzer, W, Kuemmerle, J, Jiang, S, Sirisoma, N, Kasibhatla, S, Crogan-Grundy, C, et al.. Discovery of 1-benzoyl-3-cyanopyrrolo[1,2-a] quinolines as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2: structure–activity relationships of the 4-, 5-, 6-, 7- and 8-positions. Bioorg Med Chem Lett 2009;19:3481–4. https://doi.org/10.1016/j.bmcl.2009.05.012.Search in Google Scholar PubMed

97. Al-Matarneh, MC, Amarandi, RM, Mangalagiu, II, Danac, R. Synthesis and biological screening of new cyano-substituted pyrrole fused (iso)quinoline derivatives. Molecules 2021;26:2066. https://doi.org/10.3390/molecules26072066.Search in Google Scholar PubMed PubMed Central

98. Lucas-Lopez, C, Allingham, JS, Lebl, T, Lawson, CP, Brenk, R, Sellers, JR, et al.. The small molecule tool (S)-(−)-blebbistatin: novel insights of relevance to myosin inhibitor design. Org Biomol Chem 2008;6:2076–84. https://doi.org/10.1039/b801223g.Search in Google Scholar PubMed PubMed Central

99. Lee, BD, Li, Z, French, KJ, Zhuang, Y, Xia, Z, Smith, CD. Synthesis and evaluation of dihydropyrroloquinolines that selectively antagonize P-glycoprotein. J Med Chem 2004;47:1413–22. https://doi.org/10.1021/jm0303204.Search in Google Scholar PubMed

100. Jones, AM, Patterson, S, Lorion, MM, Slawin, AMZ, Westwood, NJ. A core switching strategy to pyrrolo[2,3-b]quinolines and diazocino[1,2-a]indolinones. Org Biomol Chem 2016;14:8998–9012. https://doi.org/10.1039/c6ob01566b.Search in Google Scholar PubMed

101. Chen, K, Tang, X-Y, Shi, M. Rh(II)-catalyzed formation of pyrrolo[2,3-b]quinolines from azide-methylenecyclopropanes and isonitriles. Chem Commun 2015;52:1967–70. https://doi.org/10.1039/c5cc09236a.Search in Google Scholar PubMed

102. Akagawa, M, Nakano, M, Ikemoto, K. Recent progress in studies on the health benefits of pyrroloquinoline quinine. Biosci Biotechnol Biochem 2016;80:13–22. https://doi.org/10.1080/09168451.2015.1062715.Search in Google Scholar PubMed

103. Vlachou, M, Tsotinis, A, Kelland, LR, Thurston, DE. A new ring-forming methodology for the synthesis of bioactive pyrroloquinoline derivatives. Heterocycles 2002;57:129–33.10.3987/COM-01-9373Search in Google Scholar

104. Tsotinis, A, Vlachou, M, Zouroudis, S, Jeney, A, Timar, F, Thurston, DE, et al.. A facile synthesis of C2-substituted pyrrolo[2,3-f]quinolines with cytotoxic activity. Lett Drug Des Discov 2005;2:189–92. https://doi.org/10.2174/1570180053765075.Search in Google Scholar

105. Ferlin, MG, Gatto, B, Chiarelotto, G, Palumbo, M. Pyrrolo-quinoline derivatives as potential antineoplastic drugs. Bioorg Med Chem 2000;8:1415–22. https://doi.org/10.1016/s0968-0896(00)00060-2.Search in Google Scholar PubMed

106. Ferlin, MG, Gatto, B, Chiarelotto, G, Palumbo, M. Novel pyrrolo[3,2-f]quinolines: synthesis and antiproliferative activity. Bioorg Med Chem 2001;9:1843–8. https://doi.org/10.1016/s0968-0896(01)00071-2.Search in Google Scholar PubMed

107. Ferlin, MG, Dalla Via, L, Gia, OM. Synthesis and antiproliferative activity of some new DNA-targeted alkylating pyrroloquinolines. Bioorg Med Chem 2004;12:771–7. https://doi.org/10.1016/j.bmc.2003.10.057.Search in Google Scholar PubMed

108. Ferlin, MG, Marzano, C, Dalla Via, L, Chilin, A, Zagotto, G, Guiotto, A, et al.. New water soluble pyrroloquinoline derivatives as new potential anticancer agents. Bioorg Med Chem 2005;13:4733–9. https://doi.org/10.1016/j.bmc.2005.04.080.Search in Google Scholar PubMed

109. Ferlin, MG, Bortolozzi, R, Brun, P, Castagliuolo, I, Hamel, E, Basso, G, et al.. Synthesis and in vitro evaluation of 3H-pyrrolo[3,2-f]-quinolin-9-one derivatives that show potent and selective anti-leukemic activity. ChemMedChem 2010;5:1373–85. https://doi.org/10.1002/cmdc.201000180.Search in Google Scholar PubMed PubMed Central

110. Dalla Via, L, Gia, O, Gasparotto, V, Merlin, MG. Discovery of a new anilino-3H-pyrrolo[3,2-f]quinoline-f derivative as potential anti-cancer agent. Eur J Med Chem 2008;43:429–34. https://doi.org/10.1016/j.ejmech.2007.04.008.Search in Google Scholar PubMed

111. Dalla Via, L, Gia, O, Chiarelotto, G, Merlin, MG. DNA-targeting pyrroloquinoline-linked butenone and chalcones: synthesis and biological evaluation. Eur J Med Chem 2009;44:2854–61. https://doi.org/10.1016/j.ejmech.2008.12.011.Search in Google Scholar PubMed

112. Matesic, L, Locke, JM, Vine, KL, Ranson, M, Bremner, JB, Skropeta, D. Synthesis and anti-leukaemic activity of pyrrolo[3,2,1-hi]indole-1,2-diones, pyrrolo[3,2,1-ij]quinoline-ij-1,2-diones and other polycyclic isatin derivatives. Tetrahedron 2012;68:6810–9. https://doi.org/10.1016/j.tet.2012.06.049.Search in Google Scholar

113. Rao, MS, Haritha, M, Chandrasekhar, N, Rao, MVB, Pal, M. Ultrasound mediated synthesis of 6-substituted 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinoline-ij derivatives and their pharmacological evaluation. Arab J Chem 2019;12:2697–703. https://doi.org/10.1016/j.arabjc.2015.05.013.Search in Google Scholar

114. Zhang, H, Wu, W, Feng, C, Liu, Z, Bai, E, Wang, X, et al.. Design, synthesis, SAR discussion, in vitro and in vivo evaluation of novel selective EGFR modulator to inhibit L858R/T790M double mutants. Eur J Med Chem 2017;135:12–23. https://doi.org/10.1016/j.ejmech.2017.04.036.Search in Google Scholar PubMed

115. Ruiz, J, Ardeo, A, Ignacio, R, Sotomayor, N, Lete, E. An efficient entry to pyrrolo[1,2-b]isoquinolines and related systems through Parham cyclisation. Tetrahedron 2005;61:3311–24. https://doi.org/10.1016/j.tet.2004.10.105.Search in Google Scholar

116. Chaniyara, R, Kapuriya, N, Dong, H, Lee, PC, Suman, S, Marvania, B, et al.. Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline-b] derivatives, synthesis and biological activity. Bioorg Med Chem 2011;19:275–86. https://doi.org/10.1016/j.bmc.2010.11.030.Search in Google Scholar PubMed

117. Patel, AS, Jain, V, Rao, VN, Lin, YW, Shah, A, Lai, KC, et al.. Design, synthesis and antitumor evaluation of pyrrolo[1,2-f]phenanthridine and dibenzo[f,h]pyrrolo[1,2-b]isoquinoline b] derivatives. Eur J Med Chem 2020;202:112516. https://doi.org/10.1016/j.ejmech.2020.112516.Search in Google Scholar PubMed

118. Matveeva, MD, Purgatorio, R, Voskressensky, LG, Altomare, CD. Pyrrolo[2,1-a]isoquinoline scaffold in drug discovery: advances in synthesis and medicinal chemistry. Future Med Chem 2019;11:2735–55. https://doi.org/10.4155/fmc-2019-0136.Search in Google Scholar PubMed

119. Pässler, U, Knölker, HJ. The pyrrolo[2,1-a]isoquinoline-a] alkaloids. Alkaloids - Chem Biol 2011;70:79–151. https://doi.org/10.1016/b978-0-12-391426-2.00002-5.Search in Google Scholar PubMed

120. Lv, HN, Zeng, KW, Zhao, MB, Jiang, Y, Tu, PF. Pyrrolo[2,1-a]isoquinoline and pyrrole alkaloids from Sinomenium acutum. J Asian Nat Prod Res 2017;20:195–200. https://doi.org/10.1080/10286020.2017.1326910.Search in Google Scholar PubMed

121. Bailly, C. Anticancer properties of lamellarins. Mar Drugs 2015;13:1105–23. https://doi.org/10.3390/md13031105.Search in Google Scholar PubMed PubMed Central

122. Marco, E, Laine, W, Tardy, C, Lansiaux, A, Iwao, M, Ishibashi, F, et al.. Molecular determinants of topoisomerase I poisoning by lamellarins: comparison with camptothecin and structure–activity relationships. J Med Chem 2005;48:3796–807. https://doi.org/10.1021/jm049060w.Search in Google Scholar PubMed

123. Anderson, WK, Jr McPherson, HL, New, JS, Rick, AC. Synthesis and murine antineoplastic activity of bis[(carbamoyloxy)methyl] derivatives of pyrrolo[2,l-a]isoquinoline. J Med Chem 1984;27:1321–5. https://doi.org/10.1021/jm00376a017.Search in Google Scholar PubMed

124. Anderson, WK, Heider, AR, Raju, N, Yucht, JA. Synthesis and antileukemic activity of bis[[(carbamoyl)oxy]methyl]substituted pyrrolo[2,1-a]isoquinolines, pyrrolo[1,2-a]quinolines, pyrrolo[2,l-a]isobenzazepines, and pyrrolo[1,2-a]benzazepines. J Med Chem 1988;31:2097–102. https://doi.org/10.1021/jm00119a008.Search in Google Scholar PubMed

125. Kakhki, S, Shahosseini, S, Zarghi, A. Design, synthesis and cytotoxicity evaluation of new 2-aryl-5,6-dihydropyrrolo[2,1-a]isoquinoline derivatives as topoisomerase inhibitors. Iran J Pharm Res 2014;13:71–7.Search in Google Scholar

126. Kakhki, S, Shahosseini, S, Zarghi, A. Design and synthesis of pyrrolo[2,1-a]isoquinoline-a-based derivatives as new cytotoxic agents. Iran J Pharm Res 2016;15:743–51.Search in Google Scholar

127. Chávez-Santos, RM, Reyes-Gutiérrez, PE, Torres-Ochoa, RO, Ramirez-Apan, MT, Martinez, R. 5,6-Dihydropyrrolo[2,1-a]isoquinolines as alternative of new drugs with cytotoxic activity. Chem Pharm Bull 2017;65:973–81. https://doi.org/10.1248/cpb.c17-00409.Search in Google Scholar PubMed

128. Reyes-Gutiérrez, PE, Camacho, JR, Ramírez-Apan, MT, Osornio, YM, Martínez, R. Synthesis of 5,6-dihydropyrrolo[2,1-a]isoquinolines a] featuring an intramolecular radical-oxidative cyclization of polysubstituted pyrroles and evaluation of their cytotoxic activity. Org Biomol Chem 2010;8:4374–82. https://doi.org/10.1039/c004399k.Search in Google Scholar PubMed

129. Sano, S, Matsumoto, T, Nanataki, H, Tempaku, S, Nakao, M. Z-Selective Horner–Wadsworth–Emmons reaction of 2-TOM-cyclopentanone for the synthesis of rac-N-Cbz-Gly-Ψ[(Z)-CF=C]-Pro-OH dipeptide isostere. Tetrahedron Lett 2014;55:6248–51. https://doi.org/10.1016/j.tetlet.2014.09.077.Search in Google Scholar