Flexible Etherified and Esterified Triphenylethylene Derivatives and Their Evaluation on ER-positive and Triple-Negative Breast Cancer Cell Lines

Research output: Contribution to journalResearch articleContributedpeer-review



Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) with potential clinical benefits for all stages of breast cancer. TAM is primarily metabolized to more potent metabolites via polymorphic CYP2D6. This affects the clinical outcome of TAM treatment. Herein we report novel TAM analogues that can avoid metabolism via CYP2D6. The novel analogues bear a flexible skeleton. Compounds have either an ester group on ring C or homodiaminoalkoxy groups on rings B and C. Compound 6 (E/Z-4-[1-[4-(2-diethylaminoethoxy)phenyl]-3-(4-methoxyphenyl)-2-methyl[propenyl]phenol) was found to be ten-fold more potent than TAM on MCF-7 cells (GI50=0.15 μM). It showed fivefold greater inhibitory activity on MDA-MB-231 cells than TAM (GI50=1.71 μM). Compound 13 (4-{3,3-bis-[4-(3-dimethylaminopropoxy)phenyl]-2-methylallyl}methoxybenzene) was the most potent among the homodiaminoalkoxy derivatives (GI50=0.44) on both MCF-7 and MDA-MB-231 cell lines, respectively. Furthermore, the COMPARE algorithm suggested that it has different molecular targets from those of some other reported anticancer drugs.


Original languageEnglish
Article numbere202100720
Number of pages13
Issue number7
Publication statusPublished - 5 Apr 2022

External IDs

PubMed 35076180
WOS 000756593400001
unpaywall 10.1002/cmdc.202100720
ORCID /0000-0001-5397-7972/work/142245273


Sustainable Development Goals


  • CYP2D6, MCF-7, Ridaifen, SERM, Tamoxifen, Mcf-7, Serm, Triple Negative Breast Neoplasms, Humans, Stilbenes, MCF-7 Cells, Female, Breast Neoplasms/drug therapy, Tamoxifen/pharmacology