Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening

Nassim Borazjani, Saghi Sepehri, Maryam Behzadi, Aliasghar Jarrahpour, Javad Ameri Rad, Maryam Sasanipour, Milad Mohkam, Younes Ghasemi, Amin Reza Akbarizadeh, Carole Digiorgio, Jean Michel Brunel, Mohammad Mehdi Ghanbari, Gyula Batta, Edward Turos

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3 Citations (Scopus)

Abstract

Highly diastereoselective synthesis of chromeno β-lactam hybrids was achieved by an efficient one-pot three-component reaction. With this procedure, the desired β-lactam products were obtained in good yields and with exclusive cis stereoselection, by combining a variety of benzaldehydes, malononitrile, and either 5,5-dimethylcyclohexane-1,3-dione or 4-hydroxycoumarin in the presence of 1,4-diazabicyclo [2.2.2]octane under reflux conditions. These adducts were structurally characterized on the basis of IR, 1D and 2D NMR spectra, X-ray analysis, H–H COSY and H–C HSQC two-dimensional NMR experiments, and elemental analysis. Each of the synthesized compounds was screened for anti-inflammatory and anticancer activities. β-Lactams 5b and 8b showed a 53.4 and 19.8 anti-inflammatory ratio, respectively, and 5b appeared more active than the well-known dexamethasone corticosteroid used for the treatment of rheumatoid and skin inflammation. β-Lactams 5a, 5b, 5e, 5f, 5g, 8c, 8j and 8p also showed good antitumor activity against the SW1116 (colon cancer) cell line without notable cytotoxicity towards the HepG2 control cell line.

Original languageEnglish
Pages (from-to)389-403
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume179
DOIs
Publication statusPublished - Oct 1 2019

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Keywords

  • Anti-inflammatory
  • Anticancer
  • Colon cancer
  • Cytotoxicity
  • DABCO
  • β-Lactams

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Borazjani, N., Sepehri, S., Behzadi, M., Jarrahpour, A., Rad, J. A., Sasanipour, M., Mohkam, M., Ghasemi, Y., Akbarizadeh, A. R., Digiorgio, C., Brunel, J. M., Ghanbari, M. M., Batta, G., & Turos, E. (2019). Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening. European Journal of Medicinal Chemistry, 179, 389-403. https://doi.org/10.1016/j.ejmech.2019.06.036