Chimeric Amides of Substituted Allyl- and Phenylcarboxylic Acids with Pharmacophore Fragments of Aromatic and Heteroaromatic Rings – Potential Multitarget Protein Kinase Inhibitors: Design, Synthesis, Determination of Antitumor Activity, and In Silico Analysis

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

This study aims to synthesize and evaluate the antitumor efficacy of a series designed chimeric amides (10–14, 16, 19, 21, 25–27, 28, 30) containing various combinations of nitrogen-containing heterocycles, which are the key pharmacophores of many antitumor drugs with different mechanisms of action. The designed amides were synthesized and characterized using spectroscopic techniques. The antitumor activity of all these compounds against tumor cell lines K562 (chronic myeloid leukemia), HL-60 (acute promyelocytic leukemia), and HeLa (cervical carcinoma) was assessed in vitro in terms of the values of half-maximal inhibitory concentration (IC50). As a result, 5 lead compounds, amides (10, 11, 21, 27, 30), active against the above cell lines were identified followed by in silico analysis of their pharmacological properties and prediction of the most probable mechanism of action against myeloid blood cells K562. In light of the data obtained, the identified compounds were shown to form promising basic structures for the design of novel orally active antitumor agents, multi-target protein kinase inhibitors.

Sobre autores

E. Koroleva

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Email: evk@ichnm.by
Minsk, Belarus

Y. Sinyutich

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

A. Ermolinskaya

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

Zh. Ignatovich

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

Y. Kornoushenko

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

O. Panibrat

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

I. Katok

Belarusian State Technological University

Minsk, Belarus

A. Andrianov

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

Bibliografia

  1. Bridges A.J. // Chem. Rev. 2001. V. 101. P. 2541–2572. https://doi.org/10.1021/cr000250y
  2. Druker B.J. // Adv. Cancer Res. 2004. V. 91. P. 1–30. https://doi.org/10.1016/S0065-230X(04)91001-9
  3. Druker B.J., Guilhot F., O’Brien S.G., Gathmann I., Kantarjian H., Gattermann N., Deininger M.W.N., Silver R.T., Goldman J.M., Stone R.M., Cervantes F., Hochhaus A., Powell B.L., Gabrilove J.L., Rousselot P., Reiffers J., Cornelissen J.J., Hughes T., Agis H., Fischer T., Verhoef G., Shepherd J., Saglio G., Gratwohl A., Nielsen J.L., Radich J.P., Simonsson B., Taylor K., Baccarani M., So C., Letvak L., Larson R.A. // N. Eng. J. Med. 2006. V. 355. P. 2408–2417. https://doi.org/10.1056/NEJMoa062867
  4. Hochhaus A., Larson R.A., Guilhot F., Radich J.P., Branford S., Hughes T.P., Baccarani M., Deininger M.W., Cervantes F., Fujihara S., Ortmann C.-E., Menssen H.D., Kantarjian H., O’Brien S.G., Druker B.J. // N. Eng. J. Med. 2017. V. 376. P. 917–927. https://doi.org/10.1056/NEJMoa1609324
  5. Roskoski J.R. // Pharmacol. Res. 2024. V. 200. P. 106552. https://doi.org/10.1016/j.phys.2022.106552
  6. Cortes J., Lang F. // J. Hematol. Oncol. 2021. V. 14. P. 1–18. https://doi.org/10.1186/s13045-021-01055-9
  7. Tan F.H., Putoczki T.L., Stylii S.S., Luvor R.B. // Onco Targets Ther. 2019. V. 12. P. 635–645. https://doi.org/10.2147/OTTS189391
  8. Ferguson F.M., Gray N.S. // Nat. Rev. Drug Discov. 2018. V. 17. P. 353–377. https://doi.org/10.1038/nrd.2018.21
  9. Patel A.B., O’Hare T., Deininger M.W. // Hematol. Oncol. Clin. North Am. 2017. V. 31. P. 589–612. https://doi.org/10.1016/j.nbc.2017.04.007
  10. Liu J., Zhang Y., Huang H., Lei X., Tang G., Cao X., Peng J. // Chem. Biol. Drug Des. 2021. V. 97. P. 649–664. https://doi.org/10.1111/cbdd.13801
  11. Ma X., Lv X., Zhang J. // Eur. J. Med. Chem. 2018. V. 143. P. 449–463. https://doi.org/10.1016/j.ejmech.2017.11.049
  12. Medina-Franco J.L., Giulianotti M.A., Welmaker G.S., Houghton R.A. // Drug Discov. Today. 2013. V. 18. P. 495–501. https://doi.org/10.1016/j.drudis.2013.01.008
  13. Proschak E., Stark H., Merk D. // J. Med. Chem. 2018. V. 62. P. 420–444. https://doi.org/10.1021/acs.jmedchem.8b00760
  14. Kerru N., Singh P., Koorbanally N., Raj R., Kumar V. // Eur. J. Med. Chem. 2017. V. 142. P. 179–212. https://doi.org/10.1016/j.ejmech.2017.07.033
  15. Koroleva E.V., Ignatovich Z.I., Sinyutich Y.V., Gusak K.N. // Rus. J. Org. Chem. 2016. V. 52. P. 139–177. https://doi.org/10.1134/S1070428016020019
  16. Borsari C., Trader D.J., Tait A., Costi M.P. // J. Med. Chem. 2020. V. 63. P. 1908–1928. https://doi.org/10.1021/acs.jmedchem.9b01456
  17. Tashima T. // Bioorg. Med. Chem. Let. 2018. V. 28. P. 3015–3024. https://doi.org/10.1016/j.bmel.2018.07.012
  18. Schönherr H., Cernak T. // Angew. Chem. Int. Ed. Engl. 2013. V. 52. P. 12256–12267. https://doi.org/10.1002/anie.201303207
  19. Erri P., Altmann E., McKenna J.M. // J. Med. Chem. 2020. V. 63. P. 8408–8418. https://doi.org/10.1021/acs.jmedchem.0c00754
  20. Pennington L.D., Moustakas D.T. // J. Med. Chem. 2017. V. 60. P. 3552–3579. https://doi.org/10.1021/acs.jmedchem.6b01807
  21. Prachayastitikul S., Pingaev R., Worachartcheeva N., Sinthupom N., Prachayastitikul V., Ruchiravat S., Prachayastitikul V. // Mini Rev. Med. Chem. 2017. V. 17. P. 869–901. https://doi.org/10.2174/1389557516666160923125801
  22. Chiacchio M.A., Iannazzo D., Romeo R., Giofré S.V., Legnani L. // Curr. Med. Chem. 2019. V. 26. P. 7166–7195. https://doi.org/10.2174/0929867325666180904125400
  23. Al-Ghorbani M., Gouda M.A., Baashen M., Alharbi O., Almalki F.A., Ranganatha L.V. // Pharm. Chem. J. 2022. V. 56. P. 29–37. https://doi.org/10.1007/s11094-022-02597-z
  24. Garadachari B., Isloor A.M. // Advanced Materials Res. 2014. V. 995. P. 61–84. https://doi.org/10.4028/www.scientific.net/AMR.995.61
  25. Satija G., Sharma B., Madan A., Iqubal A., Shaquiquazaman M., Akhter M., Parvez S., Khan M.A., Alam, M.M. // J. Heterocycl. Chem. 2022. V. 59. P. 22–66. https://doi.org/10.1002/jhet.4355
  26. Yadav S., Narasimhan B. // Anticancer Agents Med. Chem. 2016. V. 16. P. 1403–1425. https://doi.org/10.2174/187152061666151103113412
  27. Meng L., Shan G., Yong W., Xinying Y., Hao F., Xuben H. // J. Med. Chem. 2024. V. 67. P. 15098–15117. https://doi.org/10.1021/acs.jmedchem.4c00729
  28. Feng L.S., Cheng J.B., Su W.Q., Li H.Z., Xiao T., Chen D.A., Zhang Z.L. // Arc. Pharm. (Weinheim). 2022. V. 355. P. e2200052. https://doi.org/10.1002/ardp.202200052
  29. De P., Baltas M., Bedos-Belval F. // Curr. Med. Chem. 2011. V. 18. P. 1672–1703. https://doi.org/10.2174/092986711795471347
  30. Fotopoulos I., Hadjipavlou-Litina D. // Exp. Opin. Drug Discov. 2024. V. 19. P. 1281–1291. https://doi.org/10.1080/17460441.2024.2387122
  31. Koroleva E.V., Ignatovich Zh.V., Ermolinskaya A.L., Sinyutich Yu.V., Tran Q. Toan // Russ. J. Org. Chem. 2021. V. 57. P. 1868–1873. https://doi.org/10.1134/S1070428021110099
  32. Deininger M.W., Vieira S., Mendiola R., Schultheis B., Goldman J.M., Melo J.V. // Cancer Res. 2000. V. 60. P. 2049–2055.
  33. Lipinski C.A. // Drug Discov. Today Technol. 2004. V. 1. P. 337–341. https://doi.org/10.1016/j.ddtec.2004.11.007
  34. Veber D.F., Johnson S.R., Cheng H.Y., Smith B.R., Ward K.W., Kopple K.D. // J. Med. Chem. 2002. V. 45. P. 2615–2623. https://doi.org/10.1021/jm020017n
  35. Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J. // Adv. Drug Deliv. Rev. 2001. V. 46. P. 3–26. https://doi.org/10.1016/s0169-409x(00)00129-0
  36. Banerjee P., Eckert A.O., Schrey A.K., Preissner R. // Nucl. Acids Res. 2018. V. 46. P.257–263. https://doi.org/10.1093/nar/gky318
  37. Lugo T.G., Pendergast A.M., Muller A.J., Witte O.N. // Science. 1990. V. 247. P. 1079–1082. https://doi.org/10.1126/science.2408149
  38. Trott O. Olson A.J. // J. Comput. Chem. 2010. V. 31. P. 455–461. https://doi.org/10.1002/jcc.21334
  39. Shen C., Hu Y., Wang Z., Zhang X., Zhong H., Wang G., Yao X., Xu L., Cao D., Hou T. // Brief. Bioinf. 2021. V. 22. P. 497–514. https://doi.org/10.1093/bib/bbz173
  40. Durrant J.D., McCammon J.A. // Chem. Inf. Model. 2011. V. 51. P. 2897–2903. https://doi.org/10.1021/ci2003889
  41. Agafonov R.V., Wilson C., Otten R., Buosi V., Kern D. // Nat. Struct. Mol. Biol. 2014. V. 21. P. 848–853. https://doi.org/10.1038/nsmb.2891
  42. Parcha P., Sarvagalla S., Madhuri B., Pajaniradje S., Baskaran V., Coumar M.S., Rajasekaran B. // Chem. Biol. Drug Des. 2017. V. 90. P. 596–608. https://doi.org/10.1111/cbdd.12983
  43. Reddy E.P., Aggarwal A.K. // Genes Cancer. 2012. V. 3. P. 447–454. https://doi.org/10.1177/1947601912462126
  44. Manley P.W., Cowan-Jacob S.W., Fendrich G., Mestan J. // Blood. 2005. V. 106. P. 3365. https://doi.org/10.1182/blood.V106.11.3365.3365
  45. Sobrady F., Bagheri M., Aliyar M., Aryapour H. // J. Mol. Graph. Model. 2017. V. 74. P. 234–240. https://doi.org/10.1016/j.jmgm.2017.04.005
  46. Is Y.S. // J. Comput. Biophys. Chem. 2021. V. 20. P. 433–447. https://doi.org/10.1142/S273741652150023X
  47. Koponescu E.B., Henamoglu R.B., Epuomuecka A.J., Cumomuv IO.B., Raphaoseckai A.B., Maxnav C.A. // Изв. НАН Беларуси. сер. хим. наук. 2013. № 3. С. 79–84.
  48. Petkevich A.V., Siniusch J.V., Martsinkevich D.S., Zdorovets M.V., Shumskaya A.E., Shahab S.N., Filippovich L.N., Ignatovich Zh.V., Rogachev A.A. // Russ. J. Gen. Chem. 2023. V. 93. Suppl. 1. P. S42–S55. https://doi.org/10.1134/S1070363223140402
  49. Koponescu E.B., Henamoglu R.B., Epuomuecka A.J., Aposecka IIIO. // Весш НАН Беларуси. сер. хим. наук. 2015. № 1. С. 63–69.
  50. Huynh T.K.C., Nguyen T., Trand N.H.S., Nguyen T.D., Hoang T.K.D. // J. Chem. Sci. 2020. V.132. P. 84–91. 10.1007/s12039-020-017834' target='_blank'>https://doi: 10.1007/s12039-020-017834
  51. Al-Nasiry S., Geusens N., Hanssen M., Luyten C., Pijnenhof R. // Hum. Reprod. 2007. V. 22. P. 1304–1309. https://doi.org/10.1093/humrep/dem011
  52. O’Boyle N.M., Bauck M., James C.A., Morley C., Vandermeersch T., Hutchison G.R. // J. Cheminform. 2011. V.3. P. 1–14. https://doi.org/10.1186/1758-2946-3-33
  53. Rappé A.K., Casewit C.J., Colwell K.S., Goddard III W.A., Skiff. W.M. // J. Am. Chem. Soc. 1992. V. 114. P. 10024–10035. https://doi.org/10.1021/ja00051a040
  54. Daina A., Michielin O., Zoete V. // Sci. Rep. 2017. V. 7. P. 42717. https://doi.org/4.2717, 10.1038/srep42717
  55. Durran J.D., McCammon J.A. // J. Mol. Graph. Model. 2011. V. 29. P. 888–893. https://doi.org/10.1016/j.jmgm.2011.01.004
  56. Petersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D. M. // J. Comput. Chem., 2004. V. 25. P. 1605–1612. https://doi.org/10.1002/jcc.20084
  57. Laskowski R.A., Swindells M.B. // J. Chem. Inform. Model. 2011. V. 51. P. 2778–2786. 10.1021/ci200227u' target='_blank'>https://doi: 10.1021/ci200227u
  58. Jimenez J.J., Chale R.S., Abad A.C., Schally A.V. // Oncotarget. 2020. V. 11. P. 992–1003. https://doi.org/10.18632/oncotarget.27513

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Russian Academy of Sciences, 2025