Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4‐Ethylenedioxythiophenyl‐2‐propen‐1‐one Analogues
| Autor: | Elangovan Vellaichamy, Hemanta K. Majumder, Jayachandran Karunakaran, Saleem Iqbal, Nachiappan Dhatchana Moorthy, Arasambattu K. Mohanakrishnan, Somenath Roy Chowdhury, Krishnasamy Gunasekaran |
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| Rok vydání: | 2019 |
| Předmět: |
Antineoplastic Agents
Apoptosis Thiophenes 01 natural sciences Biochemistry Structure-Activity Relationship chemistry.chemical_compound Drug Discovery Humans General Pharmacology Toxicology and Pharmaceutics Cytotoxicity Clonogenic assay Cell Proliferation Pharmacology chemistry.chemical_classification Molecular Structure 010405 organic chemistry Kinase Organic Chemistry HCT116 Cells 0104 chemical sciences Molecular Docking Simulation Checkpoint Kinase 2 010404 medicinal & biomolecular chemistry Enzyme chemistry Cell culture Colonic Neoplasms Cancer cell Molecular Medicine Drug Screening Assays Antitumor Divergent synthesis DNA |
| Zdroj: | ChemMedChem. 14:1418-1430 |
| ISSN: | 1860-7187 1860-7179 |
| Popis: | 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, GI50 =110 nm), 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. |
| Databáze: | OpenAIRE |
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