Везде

RAS Chemistry & Material ScienceЖурнал общей химии Russian Journal of General Chemistry

  • ISSN (Print) 0044-460X
  • ISSN (Online) 3034-5596

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

You can
PII
10.31857/S0044460X24050053-1
DOI
10.31857/S0044460X24050053
Publication type
Article
Status
Published
Authors
V. A. Sorokina
  • Occupation: <i>Institute of Biochemistry and Genetics</i>
  • Affiliation: Ufa Federal Research Center of the Russian Academy of Sciences
Volume/ Edition
Volume 94 / Issue number 5
Pages
583-592
Abstract
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.
Keywords
1 5 6 7-тетрагидроиндол-4-он реагент Лавессона цитотоксичность молекулярный докинг CDKs
Date of publication
17.09.2025
Year of publication
2025
Number of purchasers
0
Views
13

References

  1. 1. Gomtsyan A. // Chem. Heterocycl. Compd. 2012. Vol. 48. P. 7. doi 10.1007/s10593-012-0960-z
  2. 2. Sperry J.B., Wright D.L. // Curr. Opin. Drug. Discov. Devel. 2005. Vol. 8. P. 723
  3. 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. 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. 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. 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. 7. Машковский М.Д. Лекарственные средства. М.: Новая волна, 2021. 1216 c.
  8. 8. Almagro L., Fernández-Pérez F., Pedreño M.A. // Molecules. 2015. Vol. 20. P. 2973. doi 10.3390/molecules20022973
  9. 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. 10. Yu H., Jin H., Gong W., Wang Z., Liang H. // Molecules. 2013. Vol. 18. P. 1826. doi 10.3390/molecules18021826
  11. 11. Sachdeva H., Mathur J., Guleria A. // J. Chil. Chem. Soc. 2020. Vol. 65. P. 4900. doi 10.4067/s0717-97072020000204900
  12. 12. Sibel S. // Curr. Org. Chem. 2017. Vol. 21. P. 2068. doi 10.2174/1385272821666170809143233
  13. 13. Aggarwal B.B., Ichikawa H. // Cell Cycle. 2005. Vol. 4. P. 1201. doi 10.4161/cc.4.9.1993
  14. 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. 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. 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. 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. 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. 19. Badopra A.H. // J. Appl. Chem. 2018. Vol. 7. P. 299.
  20. 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. 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. 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. 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. 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. 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. 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. 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. 28. RCSB Protein Data Bank. https://www.rcsb.org
  29. 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. 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. 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. 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. 33. Ramadas S.R., Padmanabhan S. // J. Prakt. Chem. 1978. Vol. 320. P. 863. doi 10.1002/prac.19783200520
  34. 34. Khalafy J., Badparvar F., Marjani A.P. // J. Chil. Chem. Soc. 2016. Vol. 61. P. 3112. doi 10.4067/s0717-97072016000300021
  35. 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. 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. 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. 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. 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. 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. 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. 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. 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
QR
Translate

Индексирование

Scopus

Scopus

Scopus

Crossref

Scopus

Higher Attestation Commission

At the Ministry of Education and Science of the Russian Federation

Scopus

Scientific Electronic Library