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, G. Batta, Edward Turos

Research output: Contribution to journalArticle

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

Fingerprint

Lactams
Early Detection of Cancer
Screening
Inflammation
Anti-Inflammatory Agents
Benzaldehydes
Cells
Nuclear magnetic resonance
Cell Line
X ray analysis
Hep G2 Cells
Cytotoxicity
Colonic Neoplasms
Dexamethasone
Skin
Adrenal Cortex Hormones
X-Rays
Chemical analysis
Experiments

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., ... 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

Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening. / Borazjani, Nassim; Sepehri, Saghi; Behzadi, Maryam; Jarrahpour, Aliasghar; Rad, Javad Ameri; Sasanipour, Maryam; Mohkam, Milad; Ghasemi, Younes; Akbarizadeh, Amin Reza; Digiorgio, Carole; Brunel, Jean Michel; Ghanbari, Mohammad Mehdi; Batta, G.; Turos, Edward.

In: European Journal of Medicinal Chemistry, Vol. 179, 01.10.2019, p. 389-403.

Research output: Contribution to journalArticle

Borazjani, N, Sepehri, S, Behzadi, M, Jarrahpour, A, Rad, JA, Sasanipour, M, Mohkam, M, Ghasemi, Y, Akbarizadeh, AR, Digiorgio, C, Brunel, JM, Ghanbari, MM, Batta, G & Turos, E 2019, 'Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening', European Journal of Medicinal Chemistry, vol. 179, pp. 389-403. https://doi.org/10.1016/j.ejmech.2019.06.036
Borazjani, Nassim ; Sepehri, Saghi ; Behzadi, Maryam ; Jarrahpour, Aliasghar ; Rad, Javad Ameri ; Sasanipour, Maryam ; Mohkam, Milad ; Ghasemi, Younes ; Akbarizadeh, Amin Reza ; Digiorgio, Carole ; Brunel, Jean Michel ; Ghanbari, Mohammad Mehdi ; Batta, G. ; Turos, Edward. / Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 179. pp. 389-403.
@article{05c1bf30f13c4f36b0b54558b0e20758,
title = "Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening",
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.",
keywords = "Anti-inflammatory, Anticancer, Colon cancer, Cytotoxicity, DABCO, β-Lactams",
author = "Nassim Borazjani and Saghi Sepehri and Maryam Behzadi and Aliasghar Jarrahpour and Rad, {Javad Ameri} and Maryam Sasanipour and Milad Mohkam and Younes Ghasemi and Akbarizadeh, {Amin Reza} and Carole Digiorgio and Brunel, {Jean Michel} and Ghanbari, {Mohammad Mehdi} and G. Batta and Edward Turos",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.ejmech.2019.06.036",
language = "English",
volume = "179",
pages = "389--403",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Three-component synthesis of chromeno β-lactam hybrids for inflammation and cancer screening

AU - Borazjani, Nassim

AU - Sepehri, Saghi

AU - Behzadi, Maryam

AU - Jarrahpour, Aliasghar

AU - Rad, Javad Ameri

AU - Sasanipour, Maryam

AU - Mohkam, Milad

AU - Ghasemi, Younes

AU - Akbarizadeh, Amin Reza

AU - Digiorgio, Carole

AU - Brunel, Jean Michel

AU - Ghanbari, Mohammad Mehdi

AU - Batta, G.

AU - Turos, Edward

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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.

AB - 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.

KW - Anti-inflammatory

KW - Anticancer

KW - Colon cancer

KW - Cytotoxicity

KW - DABCO

KW - β-Lactams

UR - http://www.scopus.com/inward/record.url?scp=85068068172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85068068172&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2019.06.036

DO - 10.1016/j.ejmech.2019.06.036

M3 - Article

VL - 179

SP - 389

EP - 403

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -