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

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

  • Bioorg Med Chem. 2014 Mar 15;22(6):1809-20. doi: 10.1016/j.bmc.2014.01.058.
Soon Young Shin 1,  Hyeryoung Jung 2,  Seunghyun Ahn 2,  Doseok Hwang 2,  Hyuk Yoon 2,  Jiye Hyun 2,  Yeonjoong Yong 2,  Hi Jae Cho 2,  Dongsoo Koh 3,  Young Han Lee 1,  Yoongho Lim 4
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
  • 2 Division of Bioscience and Biotechnology, BMIC, Konkuk University, Hwayang-Dong 1, Kwangjin-Gu, Seoul 143-701, Republic of Korea.
  • 3 Department of Applied Chemistry, Dongduk Women's University, Seoul 136-714, Republic of Korea.
  • 4 Division of Bioscience and Biotechnology, BMIC, Konkuk University, Hwayang-Dong 1, Kwangjin-Gu, Seoul 143-701, Republic of Korea. Electronic address: yoongho@konkuk.ac.kr.
PMID: 24565968 DOI: 10.1016/j.bmc.2014.01.058
Abstract

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.

Keywords

Aurora A; Chalcone; Cinnamaldehyde; Clonogenicity; Ovarian cancer; QSAR.

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