Polyphenols bearing cinnamaldehyde scaffold showing cell growth inhibitory effects on the cisplatin-resistant A2780/Cis ovarian cancer cells

Ovarian carcinoma remains the most lethal among gynecological cancers. Chemoresistance is a clinical problem that severely limits treatment success. To identify potent anticancer agents against the cisplatin-resistant human ovarian cancer cell line A2780/Cis, 26 polyphenols bearing a cinnamaldehyde...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2014-03, Vol.22 (6), p.1809-1820
Main Authors: Shin, Soon Young, Jung, Hyeryoung, Ahn, Seunghyun, Hwang, Doseok, Yoon, Hyuk, Hyun, Jiye, Yong, Yeonjoong, Cho, Hi Jae, Koh, Dongsoo, Lee, Young Han, Lim, Yoongho
Format: Article
Language:English
Subjects:
Acrolein - analogs & derivatives
Acrolein - chemistry
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Aurora A
Cell Line, Tumor
Cell Proliferation - drug effects
Chalcone
Cinnamaldehyde
Cisplatin - pharmacology
Clonogenicity
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm - drug effects
Drug Screening Assays, Antitumor
Female
Humans
Molecular Structure
Ovarian cancer
Ovarian Neoplasms - drug therapy
Ovarian Neoplasms - pathology
Polyphenols - chemical synthesis
Polyphenols - chemistry
Polyphenols - pharmacology
QSAR
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ovarian carcinoma remains the most lethal among gynecological cancers. Chemoresistance is a clinical problem that severely limits treatment success. To identify potent anticancer agents against the cisplatin-resistant human ovarian cancer cell line A2780/Cis, 26 polyphenols bearing a cinnamaldehyde scaffold were synthesized. Structural differences in their inhibitory effect on clonogenicity of A2780/Cis cells were elucidated using comparative molecular field analysis and comparative molecular similarity indices analysis. Structural conditions required for increased inhibitory activity can be derived based on the analysis of their contour maps. The two most active compounds (16 and 19) were selected and further characterized their biological activities. We found that compounds 16 and 19 trigger cell cycle arrest at the G2/M phase and apoptotic cell death in cisplatin-resistant A2780/Cis human ovarian cancer cells. The molecular mechanism of compound 16 was elucidated using in vitro aurora A kinase assay, and the binding mode between the compound 16 and aurora A kinase was interpreted using in silico docking experiments. The findings obtained here may help us develop novel plant-derived polyphenols used for potent chemotherapeutic agents. In conclusion, compounds 16 and 19 could be used as promising lead compounds for the development of novel anticancer therapies in the treatment of cisplatin-resistant ovarian cancers.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2014.01.058