| CLEFMA-an anti-proliferative curcuminoid from structure-activity relationship studies on 3,5-bis(benzylidene)-4-piperidones. | |
| | |
MedLine Citation:
|
PMID: 20638855 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
3,5-Bis(benzylidene)-4-piperidones are being advanced as synthetic analogs of curcumin for anti-cancer and anti-inflammatory properties. We performed structure-activity relationship studies, by testing several synthesized 3,5-bis(benzylidene)-4-piperidones for anti-proliferative activity in lung adenocarcinoma H441 cells. Compared to the lead compound 1, or 3,5-bis(2-fluorobenzylidene)-4-piperidone, five compounds were found to be more potent (IC(50) < 30 microM), and 16 compounds possessed reduced cell-killing efficacy (IC(50) > 50 microM). Based on the observations, we synthesized 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2-butenoic acid] (29 or CLEFMA) as a novel analog of 1. CLEFMA was evaluated for anti-proliferative activity in H441 cells, and was found to be several folds more potent than compound 1. We did not find apoptotic cell population in flow cytometry, and the absence of apoptosis was confirmed by the lack of caspase cleavage. The electron microscopy of H441cells indicated that CLEFMA and compound 1 induce autophagic cell death that was inhibited by specific autophagy inhibitor 3-methyladenine. The results suggest that the potent and novel curcuminoid, CLEFMA, offers an alternative mode of cell death in apoptosis-resistant cancers. |
| | |
Authors:
|
Pallavi Lagisetty; Prachi Vilekar; Kaustuv Sahoo; Shrikant Anant; Vibhudutta Awasthi |
Related Documents
:
|
18202825 - The roles of poly(adp-ribose)-metabolizing enzymes in alkylation-induced cell death. 17433265 - Poly(adp-ribose) polymerase inhibition by cilostazol is implicated in the neuroprotecti... 10212235 - Glucose uptake and glycolysis reduce hypoxia-induced apoptosis in cultured neonatal rat... 11368515 - Caspase-resistant vimentin suppresses apoptosis after photodynamic treatment with a sil... 15789355 - Extracellular lysosome-associated membrane protein-1 (lamp-1) mediates autoimmune disea... 17482705 - Mxa-independent inhibition of hantaan virus replication induced by type i and type ii i... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-06-22 |
Journal Detail:
|
Title: Bioorganic & medicinal chemistry Volume: 18 ISSN: 1464-3391 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-09 Completed Date: 2010-12-06 Revised Date: 2011-08-16 |
Medline Journal Info:
|
Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
|
Languages: eng Pagination: 6109-20 Citation Subset: IM |
Copyright Information:
|
Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
|
Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenocarcinoma
/
drug therapy* Antineoplastic Agents / chemistry*, pharmacology* Autophagy / drug effects Cell Line, Tumor Cell Proliferation / drug effects* Humans Lung Neoplasms / drug therapy* Piperidones / chemistry*, pharmacology* Structure-Activity Relationship |
| Grant Support | |
ID/Acronym/Agency:
|
R03 CA143614-01/CA/NCI NIH HHS; R03 CA143614-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/3,5-bis(benzylidene)-4-piperidone; 0/Antineoplastic Agents; 0/Piperidones |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Anti-HIV and antiplasmodial activity of original flavonoid derivatives.
Next Document: Design, synthesis, and anticonvulsant activity of new N-Mannich bases derived from spirosuccinimides...