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Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4‐Ethylenedioxythiophenyl‐2‐propen‐1‐one Analogues
Author(s) -
Karunakaran Jayachandran,
Dhatchana Moorthy Nachiappan,
Chowdhury Somenath Roy,
Iqbal Saleem,
Majumder Hemanta K.,
Gunasekaran Krishnasamy,
Vellaichamy Elangovan,
Mohanakrishnan Arasambattu K.
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201900225
Subject(s) - cytotoxicity , clonogenic assay , chemistry , in vitro , topoisomerase , stereochemistry , docking (animal) , cell cycle checkpoint , cancer cell , enzyme , cell culture , cell cycle , biochemistry , cell , cancer , biology , medicine , genetics , nursing
Abstract A new series of 3,4‐ethylenedioxythiophene (EDOT)‐appended propenones were prepared by condensation reaction and their in vitro cytotoxicity effects were evaluated against five human cancer cell lines. Preliminary structure–activity relationships of EDOT‐incorporated 2‐propenone derivatives were also established. The EDOT‐appended enones demonstrated significant cytotoxicity against human cancer cell lines. The most active analogue, ( E )‐3‐(2,3‐dihydrothieno[3,4‐ b ][1,4]dioxin‐5‐yl)‐1‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one ( 3 p , GI 50 =110 n m ), severely inhibited the clonogenic potential of cancer cells, and induced cell‐cycle arrest in the G2/M phase and caused an accumulation of HCT116 colon cancer cells with >4 N DNA content. Also, 3 p exhibited weak inhibition of the enzymatic activity of human topoisomerase I. Molecular docking studies indicated preferential binding of the compounds to the ATP‐binding pocket of the human checkpoint 2 kinase (Chk2) catalytic domain, thus, identifying a novel diaryl 2‐propenone chemotype for the development of potent inhibitors of Chk2.