Synthesis and evaluation of new isatin-aminorhodanine hybrids as PIM1 and CLK1 kinase inhibitors

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Khaldoun K., Safer A., Boukabcha N., DEGE N., Ruchaud S., Souab M., ...More

JOURNAL OF MOLECULAR STRUCTURE, vol.1192, pp.82-90, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1192
  • Publication Date: 2019
  • Doi Number: 10.1016/j.molstruc.2019.04.122
  • Journal Name: JOURNAL OF MOLECULAR STRUCTURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.82-90
  • Keywords: Isatin-aminorhodanine, Microwave activation, Knoevenagel condensation, Kinase, RHODANINE DERIVATIVES, SCAFFOLD, SAR
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

A series of new hybrid isatin-aminorhodanine molecules was prepared by microwave activation under mild conditions. Unexpected condensation of isatin derivatives at C-5 position of aminorhodanine was highlighted and confirmed by NMR and X-ray analyses. The inhibitory activity of these compounds was evaluated towards eight protein kinases, CDK's-2,-5,-9; PIM-1, CLK-1, Haspin, GSK3 beta and DYRK1A, whose signaling pathway dysregulation is associated to multifactorial diseases such as cancer, inflammatory, cardiovascular, and neurodegenerative diseases. Compound 3l bearing a bromo substituent has shown a potent and selective Pim1 kinase inhibitor activity. (C) 2019 Elsevier B.V. All rights reserved.