Dimeric 3,5-bis(benzylidene)-4-piperidones: A novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties

Swagatika Das, Umashankar Das, Hiroshi Sakagami, Naoki Umemura, Shoko Iwamoto, Tomohiko Matsuta, Masami Kawase, J. Molnár, Julianna Serly, Dennis K J Gorecki, Jonathan R. Dimmock

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

A series of bis[3,5-bis(benzylidene)-4-oxo-1-piperidinyl]amides 1 display potent cytotoxic properties towards a wide range of tumours. A number of the CC 50 and IC 50 values are in the range of 10 -8 M. Specifically, these compounds have the following important properties. First, greater toxicity was demonstrated towards certain tumours than various non-malignant cells. Second, various compounds in series 1 are toxic to a number of human colon cancer and leukaemic cells. Third, these compounds reverse P-gp mediated multidrug resistance. Various prototypic molecules such as 1a,b and 1i were identified as lead molecules for further studies. A representative lead molecule 1b induces apoptosis via internucleosomal DNA fragmentation and PARP cleavage in HSC-2 and HL-60 cells while flow cytometry revealed that this compound blocked the G2/M and S-phases in the cell cycle of human colon cancer HCT-116 cells.

Original languageEnglish
Pages (from-to)193-199
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume51
DOIs
Publication statusPublished - May 2012

Fingerprint

Cytotoxins
Colonic Neoplasms
Tumors
HCT116 Cells
Molecules
Poisons
HL-60 Cells
Multiple Drug Resistance
DNA Fragmentation
S Phase
Amides
Cell Division
Neoplasms
Cell Cycle
Flow Cytometry
Flow cytometry
Apoptosis
Toxicity
Display devices
Cells

Keywords

  • α,β-Unsaturated ketones
  • Cytotoxicity
  • MDR-revertants
  • Structure-activity relationships
  • Tumour-selectivity

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Dimeric 3,5-bis(benzylidene)-4-piperidones : A novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties. / Das, Swagatika; Das, Umashankar; Sakagami, Hiroshi; Umemura, Naoki; Iwamoto, Shoko; Matsuta, Tomohiko; Kawase, Masami; Molnár, J.; Serly, Julianna; Gorecki, Dennis K J; Dimmock, Jonathan R.

In: European Journal of Medicinal Chemistry, Vol. 51, 05.2012, p. 193-199.

Research output: Contribution to journalArticle

Das, Swagatika ; Das, Umashankar ; Sakagami, Hiroshi ; Umemura, Naoki ; Iwamoto, Shoko ; Matsuta, Tomohiko ; Kawase, Masami ; Molnár, J. ; Serly, Julianna ; Gorecki, Dennis K J ; Dimmock, Jonathan R. / Dimeric 3,5-bis(benzylidene)-4-piperidones : A novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties. In: European Journal of Medicinal Chemistry. 2012 ; Vol. 51. pp. 193-199.
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