Dimeric 3,5-bis(benzylidene)-4-piperidones: A novel cluster of tumour-selective cytotoxins possessing multidrug-resistant properties
| Autor: | Shoko Iwamoto, Tomohiko Matsuta, Umashankar Das, Dennis K.J. Gorecki, Swagatika Das, Jonathan R. Dimmock, Julianna Serly, Naoki Umemura, Masami Kawase, Hiroshi Sakagami, Joseph Molnár |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pharmacology
medicine.diagnostic_test Stereochemistry Chemistry Organic Chemistry Antineoplastic Agents General Medicine Cell cycle Drug Resistance Multiple Flow cytometry Multiple drug resistance Inhibitory Concentration 50 Apoptosis Cell Line Tumor Drug Discovery Toxicity medicine Humans Cytotoxic T cell DNA fragmentation Cytotoxicity Dimerization Piperidones Cell Proliferation |
| Zdroj: | European Journal of Medicinal Chemistry. 51:193-199 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2012.02.042 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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