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Synthesis, biological evaluation, and molecular docking studies of substituted chromone-2-carboxamide derivatives as anti-breast cancer agents Cover

Synthesis, biological evaluation, and molecular docking studies of substituted chromone-2-carboxamide derivatives as anti-breast cancer agents

Open Access
|Sep 2025

References

  1. Tran KB, Lang JJ, Compton K, Xu R, Acheson AR, Henrikson HJ, et al. The global burden of cancer attributable to risk factors, 2010–19: A systematic analysis for the global burden of disease study 2019. Lancet. 2022;400(10352):563–91. 10.1016/S0140-6736(22)01438-6.
  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. 10.3322/caac.21660.
  3. Keri RS, Budagumpi S, Pai RK, Balakrishna RG. Chromones as a privileged scaffold in drug discovery: A review. Eur J Med Chem. 2014;78:340–74. 10.1016/j.ejmech.2014.03.047.
  4. Gaspar A, Matos MJ, Garrido J, Uriarte E, Borges F. Chromone: A valid scaffold in medicinal chemistry. Chem Rev. 2014;114(9):4960–92. 10.1021/cr400265z.
  5. Gomes LR, Low JN, Cagide F, Gaspar A, Reis J, Borges F. Structural characterization of some N-phenyl-4-oxo-4H-2-chromone carboxamides. Acta Crystallogr B Struct Sci Cryst Eng Mater. 2013;69(Pt 3):294–309. 10.1107/S2052519213009676.
  6. Shaveta, Singh A, Kaur M, Sharma S, Bhatti R, Singh P. Rational design, synthesis and evaluation of chromone-indole and chromone-pyrazole based conjugates: Identification of a lead for anti-inflammatory drug. Eur J Med Chem. 2014;77:185–92. 10.1016/j.ejmech.2014.03.003.
  7. Patil VM, Masand N, Verma S, Masand V. Chromones: Privileged scaffold in anticancer drug discovery. Chem Biol Drug Des. 2021;98(5):943–53. 10.1111/cbdd.13951.
  8. Nam DH, Lee KY, Moon CS, Lee YS. Synthesis and anticancer activity of chromone-based analogs of lavendustin A. Eur J Med Chem. 2010;45(9):4288–92. 10.1016/j.ejmech.2010.06.030.
  9. Kim SH, Lee YH, Jung SY, Kim HJ, Jin C, Lee YS. Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties. Eur J Med Chem. 2011;46(5):1721–8. 10.1016/j.ejmech.2011.02.025.
  10. Anjum NF, Aleem A, Nayeem N, Asdaq SM. Synthesis and antibacterial activity of substituted 2-phenyl-4-chromones. Der Pharm Chem. 2011;3(5):56–62.
  11. Raju BC, Rao RN, Suman P, Yogeeswari P, Sriram D, Shaik TB, et al. Synthesis, structure-activity relationship of novel substituted 4H-chromen-1,2,3,4-tetrahydropyrimidine-5-carboxylates as potential anti-mycobacterial and anticancer agents. Bioorg Med Chem Lett. 2011;21(10):2855–9. 10.1016/j.bmcl.2011.03.079.
  12. Kim MK, Yoon H, Barnard DL, Chong Y. Design, synthesis and antiviral activity of 2-(3-amino-4-piperazinylphenyl)chromone derivatives. Chem Pharm Bull (Tokyo). 2013;61(4):486–8. 10.1248/cpb.c12-01050.
  13. Dengle RV, Deshmukh RN. Synthesis and antimicrobial evaluation of chromones bearing 1, 5-benzo thiazepinyl moiety. Int J Pharml Sci Res. 2013;4:1495–8. 10.13040/IJPSR.0975-8232.4(4).1495-98.
  14. Gaspar A, Teixeira F, Uriarte E, Milhaze N, Melo A, Cordeiro MN, et al. Towards the discovery of a novel class of monoamine oxidase inhibitors: Structure–Property–Activity and docking studies on chromone amides. Chem Med Chem. 2011;6(4):628–32. 10.1002/cmdc.201000452.
  15. Reis J, Gaspar A, Milhazes N, Borges F. Chromone as a privileged scaffold in drug discovery: recent advances: Miniperspective. J Med Chem. 2017;60(19):7941–57. 10.1021/acs.jmedchem.6b01720.
  16. Rao YJ, Abhijit K, Mallikarjun G, Hemasri Y. Design and synthesis of novel benzyloxy-tethered-chromone-carboxamide derivatives as potent and selective human monoamine oxidase-b inhibitors. Chem Pap. 2021;75:703–16. org/10.1007/s11696-020-01332-w.
  17. Alcaro S, Gaspar A, Ortuso F, Milhazes N, Orallo F, Uriarte E, et al. Chromone-2- and -3-carboxylic acids inhibit differently monoamine oxidases A and B. Bioorg Med Chem Lett. 2010;20(9):2709–12. 10.1016/j.bmcl.2010.03.081.
  18. Gaspar A, Reis J, Fonseca A, Milhazes N, Viña D, Uriarte E, et al. Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors. Bioorg Med Chem Lett. 2011;21(2):707–9. 10.1016/j.bmcl.2010.11.128.
  19. Cagide F, Silva T, Reis J, Gaspar A, Borges F, Gomes LR, et al. Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry. Chem Commun (Camb). 2015;51(14):2832–5. 10.1039/c4cc08798d.
  20. Cagide F, Gaspar A, Reis J, Chavarria D, Vilar S, Hripcsak G, et al. Navigating in chromone chemical space: discovery of novel and distinct A3 adenosine receptor ligands. RSC Adv. 2015;5:78572–85. 10.1039/C5RA14988F.
  21. Gaspar A, Reis J, Kachler S, Paoletta S, Uriarte E, Klotz KN, et al. Discovery of novel A3 adenosine receptor ligands based on chromone scaffold. Biochem Pharmacol. 2012;84(1):21–9. 10.1016/j.bcp.2012.03.007.
  22. Osborne CK, Schiff R, Arpino G, Lee AS, Hilsenbeck VG. Endocrine responsiveness: Understanding how progesterone receptor can be used to select endocrine therapy. Breast. 2005;14(6):458–65. 10.1016/j.breast.2005.08.024.
  23. Johnston S. Fulvestrant and the sequential endocrine cascade for advanced breast cancer. Br J Cancer. 2004;90(Suppl 1):S15–8. 10.1038/sj.bjc.6601632.
  24. Jordan VC. The role of Tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer. 1992;16(3):129–76. 10.1016/0147-0272(92)90002-6.
  25. Seema B, Shakti S, Puneet K, Swati K, Manan KD, Akshara S, et al. Synthesis and docking studies on styryl chromones exhibiting cytotoxicity in human breast cancer cell line. Bioorg Med Chem Lett. 2010;20(16):4945–50. org/10.1016/j.bmcl.2010.05.108.
  26. Ettinger B. Overview of estrogen replacement therapy: a historical perspective. Proc Soc Exp Biol Med. 1998;217(1):2–5. 10.3181/00379727-217-44198.
  27. Frasor J, Stossi F, Danes JM, Komm B, Lyttle CR, Katzenellenbogen BS. Selective estrogen receptor modulators: discrimination of agonistic versus antagonistic activities by gene expression profiling in breast cancer cells. Cancer Res. 2004;64(4):1522–33. 10.1158/0008-5472.can-03-3326.
  28. Sui M, Huang Y, Park BH, Davidson NE, Fan W. Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel through inhibition of apoptotic cell death. Cancer Res. 2007;67(11):5337–44. 10.1158/0008-5472.CAN-06-4582.
  29. Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, et al. Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology. 1997;138(3):863–70. 10.1210/endo.138.3.4979.
  30. Seeger H, Huober J, Wallwiener D, Mueck AO. Inhibition of human breast cancer cell proliferation with estradiol metabolites is as effective as with Tamoxifen. Horm Metab Res. 2004;36(5):277–80. 10.1055/s-2004-814480.
  31. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90(18):1371–88. 10.1093/jnci/90.18.1371.
  32. Phillips DH, Venitt S. Safety of prophylactic Tamoxifen. Lancet. 1993;341(8858):1485–6. 10.1016/0140-6736(93)90934-9.
  33. Jordan VC. Tamoxifen: A most unlikely pioneering medicine. Nat Rev Drug Discov. 2003;2(3):205–13. 10.1038/nrd1031.
  34. Hussain MK, Ansari MI, Yadav N, Gupta PK, Gupta AK, Saxena R, et al. Design and synthesis of ERα/ERβ selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents. RSC Adv. 2014;4:8828–45. 10.1039/C3RA45749D.
  35. Saquib M, Baig MH, Khan MF, Azmi S, Khatoon S, Rawat AK, et al. Design and synthesis of bioinspired benzocoumarin-chalcones chimeras as potential anti-breast cancer agents. ChemistrySelect. 2021;6:8754–65. 10.1002/slct.202101853.
  36. Tong YF, Chen S, Cheng YH, Wu S. A convenient synthesis of 6-demethoxycapillarisin. Chin Chem Lett. 2007;18(4):407–8. 10.1016/j.cclet.2007.01.049.
  37. Zagorevskii VA, Zykov DA, Orliva EK. Synthesis of Chromone-2-carboxylic Acids and Their Esters. J Gen Chem USSR. 1960;30(12):3850–94.
  38. Paulvannan K, Hale R, Mesis R, Chen T. Tandem N-acyliminium/Pictet–Spengler/intramolecular Diels–Alder reaction: an expedient route to hexacyclic tetrahydro-β-carbolines. Tetrahedron Lett. 2002;43(2):203–7. 10.1016/S0040-4039(01)02074-3.
  39. Lynch JK, Freeman JC, Judd AS, Iyengar R, Mulhern M, Zhao G, et al. Optimization of chromone-2-carboxamide melanin concentrating hormone receptor 1 antagonists: assessment of potency, efficacy, and cardiovascular safety. J Med Chem. 2006;49(22):6569–84. 10.1021/jm060683e.
  40. Crouch SP, Kozlowski R, Slater KJ, Fletcher J. The use of ATP bioluminescence as a measure of cell proliferation and cytotoxicity. J Immunol Methods. 1993;160:81–8. 10.1016/0022-1759(93)90011-u.
  41. Gangapuram M, Eyunni S, Redda KK. Synthesis and pharmacological evolution of tetrahydroisoquinolines as anti breast cancer agents. J Cancer Sci Ther. 2014;6:161–9. 10.4172/1948-5956.1000266.
  42. Suresh VK, Madhavi G, Redda KK. In-vitro antiproliferative activity of new tetrahydroisoquinolines (THIQs) on Ishikawa cells and their 3D pharmacophore models. Lett Drug Des Discov. 2014;11:428–36. 10.2174/1570180811666131203002502.
  43. Schrödinger Release 2024-1: Maestro. New York, NY: Schrödinger, LLC;s 2024.
  44. McCullough C, Neumann TS, Gone JR, He Z, Herrild C, Wondergem Nee Lukesh J, et al. Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: A combined synthesis, binding and docking study. Bioorg Med Chem. 2014;22(1):303–10. 10.1016/j.bmc.2013.11.024.
Language: English
Submitted on: Aug 28, 2024
Accepted on: May 21, 2025
Published on: Sep 11, 2025
Published by: Sciendo
In partnership with: Paradigm Publishing Services

© 2025 Madhavi Gangapuram, Mohammad A. Ghaffari, Suresh Eyunni, Bereket Mochona, Kinfe Ken Redda, published by Sciendo
This work is licensed under the Creative Commons Attribution 4.0 License.