Cholecystokinin-1 receptor antagonists

5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents

E. Lattmann, S. T. Russell, C. H. Schwalbe, A. Shortt, P. N. Balaram, E. Theochari, M. Alharbi, Ramesh Narayanan, P. Lattmann

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

A new class of 5-arylated 5-hydroxypyrrolones was derived from mucochloric acid in 2 synthetic steps and the chemical structure was confirmed additionally by X-ray analysis. Using a radiolabelled binding assay, potent CCK1 selective ligands were identified (CCK1: 12 nM) and the antagonism was confirmed by using isolated tissue preparations. A series of isobutyl derivatives displayed unsurmountable CCK antagonistic properties and in vitro excellent inhibition of proliferation was obtained in cholecystokinin related cancer cell lines in the nanomolar range. Finally, using xenograft studies in nude mice, two selected pyrrolone derivatives, X = H and X = F a fluorinated analogue (PNB-028), showed a strong inhibition of tumour growth in a chemo-resistant colon cancer-(MAC 16) and a human pancreatic cell line (MIAPACA) at 50 mg kg-1 by oral administration.

Original languageEnglish (US)
Pages (from-to)1138-1145
Number of pages8
JournalMedChemComm
Volume7
Issue number6
DOIs
StatePublished - Jan 1 2016

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Cholecystokinin Receptors
Cholecystokinin
Antineoplastic Agents
Cells
Derivatives
Cell Line
X ray analysis
Heterografts
Nude Mice
Colonic Neoplasms
Oral Administration
Tumors
Assays
Neoplasms
X-Rays
Tissue
Ligands
Growth
mucochloric acid
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Cite this

Lattmann, E., Russell, S. T., Schwalbe, C. H., Shortt, A., Balaram, P. N., Theochari, E., ... Lattmann, P. (2016). Cholecystokinin-1 receptor antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents. MedChemComm, 7(6), 1138-1145. https://doi.org/10.1039/c6md00052e

Cholecystokinin-1 receptor antagonists : 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents. / Lattmann, E.; Russell, S. T.; Schwalbe, C. H.; Shortt, A.; Balaram, P. N.; Theochari, E.; Alharbi, M.; Narayanan, Ramesh; Lattmann, P.

In: MedChemComm, Vol. 7, No. 6, 01.01.2016, p. 1138-1145.

Research output: Contribution to journalArticle

Lattmann, E, Russell, ST, Schwalbe, CH, Shortt, A, Balaram, PN, Theochari, E, Alharbi, M, Narayanan, R & Lattmann, P 2016, 'Cholecystokinin-1 receptor antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents', MedChemComm, vol. 7, no. 6, pp. 1138-1145. https://doi.org/10.1039/c6md00052e
Lattmann E, Russell ST, Schwalbe CH, Shortt A, Balaram PN, Theochari E et al. Cholecystokinin-1 receptor antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents. MedChemComm. 2016 Jan 1;7(6):1138-1145. https://doi.org/10.1039/c6md00052e
Lattmann, E. ; Russell, S. T. ; Schwalbe, C. H. ; Shortt, A. ; Balaram, P. N. ; Theochari, E. ; Alharbi, M. ; Narayanan, Ramesh ; Lattmann, P. / Cholecystokinin-1 receptor antagonists : 5-hydroxy-5-aryl-pyrrol-2-ones as anticancer agents. In: MedChemComm. 2016 ; Vol. 7, No. 6. pp. 1138-1145.
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