J Appl Biomed 13:305-317, 2015 | DOI: 10.1016/j.jab.2015.05.001

Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells

Chawannuch Mudjupaa, Sherif Abdelhamedb, Alaa Refaatb, Satoru Yokoyamab, Ikuo Saikib, Opa Vajraguptaa,c,*
a Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudya Road, Bangkok 10400, Thailand
b Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
c Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudya Road, Bangkok 10400, Thailand

A small molecule EGFR inhibitor, 4-(2-(3-(4-(4-(trifluoromethyl)phenyl)thiazol-2-yl)ureido)vinyl)-1,2-phenylene diacetate (

CIU1) was designed in silico by using caffeic scaffold as core structure. The designed compound showed anti-proliferative action against different solid tumor cell lines, particularly metastatic breast cancer cells.

CIU1 inhibited the growth of EGFR-overexpressing MDA-MB-468 triple-negative breast cancer cells and wild-type non-small-cell lung cancer H460 cells with IC50 values of 8.96 μM and 12.98 μM, respectively, these anti-proliferative effects of

CIU1 were comparable to gefitinib (a specific EGFR inhibitor) or lapatinib (a dual EGFR and HER2 tyrosine kinase inhibitor). Interestingly

CIU1 effectively inhibited the invasive hormone-dependent MCF-7 cancer cells with an IC50 2.34 μM. The immunoblot analyses revealed that

CIU1 induced programmed cell death and suppressed EGFR expression in EGFR-overexpressing breast cancer (MDA-MB468) and lung cancer (PC-9) cells. The findings substantiated our design strategy and demonstrated the potential of

CIU1 as new lead for further optimization in the development of anticancer drugs against advanced solid tumors.

Keywords: Caffeic acid derivatives; EGFR inhibitor; Triple-negative breast cancer; Non-small cell lung cancer; Molecular modeling

Received: January 29, 2015; Revised: May 15, 2015; Accepted: May 21, 2015; Published: November 1, 2015  Show citation

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Mudjupa C, Abdelhamed S, Refaat A, Yokoyama S, Saiki I, Vajragupta O. Lead compound bearing caffeic scaffold induces EGFR suppression in solid tumor cancer cells. J Appl Biomed. 2015;13(4):305-317. doi: 10.1016/j.jab.2015.05.001.
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