Synthesis and cytotoxic activity of 1,5,6,7-tetrahydroindol-4-one derivatives and its thio analogue

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

Derivatives of 1,5,6,7-tetrahydroindol-4-one and its thio analogue were synthesized and their cytotoxicity against HEK293, Jurkat and MCF-7 cells was investigated in vitro. The hit compound, 6,6-dimethyl-1-(2-methylphenyl)-2-phenyl-1,5,6,7-tetrahydro-4H-indol-4-one, was found to inhibit the metabolic activity of lymphoblastic leukemia cells (Jurkat) with IC50 = 14.8 µM and normal human embryonic kidney cells (HEK293) with IC50 = 93.63 µM. The proposed mechanism of cytotoxic action of the most active compound was shown in silico to be mediated by interaction with the cyclin-dependent kinase CDK9 site.

Texto integral

Acesso é fechado

Sobre autores

V. Sorokina

Ufa Federal Research Center of the Russian Academy of Sciences

Autor responsável pela correspondência
Email: tsypysheva.ip@gmail.com
ORCID ID: 0000-0001-5311-9580

Ufa Institute of Chemistry

Rússia, Ufa

D. Tsypyshev

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID ID: 0000-0003-4551-0226

Ufa Institute of Chemistry

Rússia, Ufa

A. Koval’skaya

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID ID: 0000-0001-7772-2894

Ufa Institute of Chemistry

Rússia, Ufa

V. Vakhitov

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID ID: 0000-0001-8805-9872

Institute of Biochemistry and Genetics

Rússia, Ufa

I. Tsypysheva

Ufa Federal Research Center of the Russian Academy of Sciences

Email: tsypysheva.ip@gmail.com
ORCID ID: 0000-0002-5025-8742

Institute of Biochemistry and Genetics

Rússia, Ufa

Bibliografia

  1. Gomtsyan A. // Chem. Heterocycl. Compd. 2012. Vol. 48. P. 7. doi: 10.1007/s10593-012-0960-z
  2. Sperry J.B., Wright D.L. // Curr. Opin. Drug. Discov. Devel. 2005. Vol. 8. P. 723
  3. Shiro T, Fukaya T, Tobe M. // Eur. J. Med. Chem. 2015. Vol. 97. P. 397. doi: 10.1016/j.ejmech.2014.12.004
  4. Huigens R.W. 3rd, Brummel B.R., Tenneti S., Garrison A.T., Xiao T. // Molecules. 2022. Vol. 27. P. 1112. doi: 10.3390/molecules27031112
  5. Raffa D. Maggio B., Raimondi M.V., Cascioferro S., Plescia F., Cancemi G., Daidone G. // Eur. J. Med. Chem. 2015. Vol. 97. P. 732. doi: 10.1016/j.ejmech.2014.12.023
  6. Afzal O., Kumar S., Haider M.R., Ali M.R., Kumar R., Jaggi M., Bawa S. // Eur. J. Med. Chem. 2015. Vol. 97. P. 871. doi: 10.1016/j.ejmech.2014.07.044
  7. Машковский М.Д. Лекарственные средства. М.: Новая волна, 2021. 1216 c.
  8. Almagro L., Fernández-Pérez F., Pedreño M.A. // Molecules. 2015. Vol. 20. P. 2973. doi: 10.3390/molecules20022973
  9. Fernández-Pérez F., Almagro L., Pedreño M.A., Gómez Ros L.V. // Pharm. Biol. 2013. Vol. 51. P. 304. doi: 10.3109/13880209.2012.722646
  10. Yu H., Jin H., Gong W., Wang Z., Liang H. // Molecules. 2013. Vol. 18. P. 1826. doi: 10.3390/molecules18021826
  11. Sachdeva H., Mathur J., Guleria A. // J. Chil. Chem. Soc. 2020. Vol. 65. P. 4900. doi: 10.4067/s0717-97072020000204900
  12. Sibel S. // Curr. Org. Chem. 2017. Vol. 21. P. 2068. doi: 10.2174/1385272821666170809143233
  13. Aggarwal B.B., Ichikawa H. // Cell Cycle. 2005. Vol. 4. P. 1201. doi: 10.4161/cc.4.9.1993
  14. Jia Y., Wen X., Gong Y., Wang X. // Eur. J. Med. Chem. 2020. Vol. 200. P. 112359. doi: 10.1016/j.ejmech.2020.112359
  15. Hong Y., Zhu Y.Y., He Q., Gu S.X. // Bioorg. Med. Chem. 2022. Vol. 55. P. 116597. doi: 10.1016/j.bmc.2021.116597
  16. Kaur B., Venugopal S., Verma A., Sahu S.K., Wadhwa P., Kumar D., Sharma A. // Curr. Org. Synth. 2023. Vol. 20. P. 376. doi: 10.2174/1570179419666220509215722
  17. Wan Y., Li Y., Yan C., Yan M., Tang Z. // Eur. J. Med. Chem. 2019. Vol. 183. P. 111691. doi: 10.1016/j.ejmech.2019.111691
  18. Asati V., Bhupal R., Bhattacharya S., Kaur K., Gupta G.D., Pathak A., Mahapatra D.K. // Anticancer Agents Med. Chem. 2023. Vol. 23. P. 404. doi 10.2174/ 1871520622666220607143040
  19. Badopra A.H. // J. Appl. Chem. 2018. Vol. 7. P. 299.
  20. Choi S.J., Lee J.E., Jeong S.Y., Im I., Lee S.D., Lee E.J., Lee S.K., Kwon S.M., Ahn S.G., Yoon J.H., Han S.Y., Kim J.I., Kim Y.C. // J. Med. Chem. 2010. Vol. 53. P. 3696. doi: 10.1021/jm100080z
  21. Jacquemard U., Dias N., Lansiaux A., Bailly C., Logé C., Robert J.M., Lozach O., Meijer L., Mérour J.Y., Routier S. // Bioorg. Med. Chem. 2008. Vol. 16. P. 4932. doi: 10.1016/j.bmc.2008.03.034
  22. Choi S.J., Lee J.E., Jeong S.Y., Im I., Lee S.D., Lee E.J., Lee S.K., Kwon S.M., Ahn S.G., Yoon J.H., Han S.Y., Kim J.I., Kim Y.C. // J. Med. Chem. 2010. Vol. 53. P. 3696. doi: 10.1021/jm100080z
  23. Martinez R., Avila-Zarraga G., Ramirez M.T., Perez A. // Arkivoc. 2003. N 11. P. 48. doi: 10.3998/ark.5550190.0004.b06
  24. Martínez R., Avila J.G., Ramírez M.T., Pérez A., Martínez A. // Bioorg. Med. Chem. 2006. Vol. 14. P. 4007. doi: 10.1016/j.bmc.2006.02.012
  25. Martínez R., Clara-Sosa A., Ramírez Apan M.T. // Bioorg. Med. Chem. 2007. Vol. 15. P. 3912. doi 10.1016/ j.bmc.2006.12.018
  26. Martínez R., Arzate M.M., Ramírez-Apan M.T. // Bioorg. Med. Chem. 2009. Vol. 17. P. 1849. doi 10.1016/ j.bmc.2009.01.056
  27. Сорокина В.А., Цыпышев Д.О., Ковальская А.В., Цыпышева И.П. // Вестн. Башкирск. унив. 2021. Т. 26. С. 304. doi: 10.33184/bulletin-bsu-2021.2.6
  28. RCSB Protein Data Bank. https://www.rcsb.org
  29. Schonbrunn E., Betzi S., Alam R., Martin M.P., Becker A., Han H., Francis R., Chakrasali R., Jakkaraj S., Kazi A., Sebti S.M., Cubitt C.L., Gebhard A.W., Hazlehurst L.A., Tash J.S., Georg G.I. // J. Med. Chem. 2013. Vol. 56. P. 3768. doi: 10.1021/jm301234k
  30. Ahn J.S., Radhakrishnan M.L., Mapelli M., Choi S., Tidor B., Cuny G.D., Musacchio A., Yeh L.A., Kosik K.S. // Chem. Biol. 2005. Vol. 12. P. 811. doi: 10.1016/j.chembiol.2005.05.011
  31. Bettayeb K., Baunbæk D., Delehouze C., Loaëc N., Hole A.J., Baumli S., Endicott J.A., Douc-Rasy S., Bénard J., Oumata N., Galons H., Meijer L. // Genes Cancer. 2010. Vol. 1. P. 369. doi: 10.1177/1947601910369817
  32. Положенцева И.А., Ковальская А.В., Цыпышев Д.О., Лобов А.Н., Назаров А.М., Данилко К.В., Катаев В.А. // Баш. хим. ж. 2018. Том 25. С. 59. doi: 10.17122/bcj-2018-1-59-66
  33. Ramadas S.R., Padmanabhan S. // J. Prakt. Chem. 1978. Vol. 320. P. 863. doi: 10.1002/prac.19783200520
  34. Khalafy J., Badparvar F., Marjani A.P. // J. Chil. Chem. Soc. 2016. Vol. 61. P. 3112. doi: 10.4067/s0717-97072016000300021
  35. Koval’skaya A.V., Petrova P.R., Tsypyshev D.O., Lobov A.N., Tsypysheva I.P. // Nat. Prod. Res. 2022. Vol. 36. P. 3538. doi: 10.1080/14786419.2020.1868460
  36. Schrödinger Release 2018-1: Maestro, Schrödinger, LLC, New York, 2018 (демо-версия от 03.03.2021 для ФГБУ «Институт фармакологии им. А.В. Закусова», Москва)
  37. Harder E., Damm W., Maple J., Wu C., Reboul M., Xiang J.Y., Wang L., Lupyan D., Dahlgren M.K., Knight J.L., Kaus J.W., Cerutti D.S., Krilov G., Jorgensen W.L., Abel R., Friesner R.A. // J. Chem. Theory. Comput. 2016. Vol. 12. P. 281. doi: 10.1021/acs.jctc.5b00864
  38. Sastry G.M., Adzhigirey M., Day T., Annabhimoju R., Sherman W. // J. Comput. Aided Mol. Des. 2013. Vol. 27. P. 221. doi: 10.1007/s10822-013-9644-8
  39. Jacobson M.P., Pincus D.L., Rapp C.S., Day T.J., Honig B., Shaw D.E., Friesner R.A. // Proteins. 2004. Vol. 55. P. 351. doi: 10.1002/prot.10613
  40. Jacobson M.P., Friesner R.A., Xiang Z., Honig B. // J. Mol. Biol. 2002. Vol. 320. P. 597. doi: 10.1016/s0022-2836(02)00470-9
  41. Friesner R.A., Murphy R.B., Repasky M.P., Frye L.L., Greenwood J.R., Halgren T.A., Sanschagrin P.C., Mainz D.T. // J. Med. Chem. 2006. Vol. 49. P. 6177. doi: 10.1021/jm051256o
  42. Halgren T.A., Murphy R.B., Friesner R.A., Beard H.S., Frye L.L., Pollard W.T., Banks J.L. // J. Med. Chem. 2004. Vol. 47. P. 1750. doi: 10.1021/jm030644s
  43. Friesner R.A., Banks J.L., Murphy R.B., Halgren T.A., Klicic J.J., Mainz D.T., Repasky M.P., Knoll E.H., Shelley M., Perry J.K., Shaw D.E., Francis P., Shenkin P.S. // J. Med. Chem. 2004. Vol. 47. P. 1739. doi: 10.1021/jm0306430

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Fig. 1. Evaluation of the effect of compound 3 on cell cycle progression of HEK293, MCF-7, and Jurkat cells. Cells with the test compound at the IC50 concentration determined for each cell line were incubated for 24 (a), 48 (b), 72 hours (c). Data obtained from two independent experiments (N = 2, n = 6) are presented as mean ± standard deviation; * – p < 0.05 (Wilcoxon t-test).

Baixar (346KB)
Metadados
3. Fig.2. Docking poses of derivative 3 (a) and reference ligand S-CR8 (b) at the 3LQ5 CDK9 binding site; hydrogen bonds are indicated by dotted lines.

Baixar (392KB)
Metadados
4. Scheme 1.

Baixar (129KB)
Metadados
5. Scheme 2.

Baixar (128KB)
Metadados
6. Scheme 3.

Baixar (51KB)
Metadados

Declaração de direitos autorais © Russian Academy of Sciences, 2024