Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4-Ethylenedioxythiophenyl-2-propen-1-one Analogues.

Autor: Karunakaran J; Department of Organic Chemistry, School of Chemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India., Dhatchana Moorthy N; Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India.; Department of Biotechnology, Orchid Pharma Limited, Orchid Towers #313, Valluvar Kottam High Road, Nungambakkam, Chennai, 600034, Tamil Nadu, India., Chowdhury SR; Division of Infectious Diseases & Immunology, Indian Institute of Chemical Biology, 4, Raja S. C. Mallick Road, Jadavpur, Kolkata, 700032, West Bengal, India., Iqbal S; Center for Advanced studies in Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India., Majumder HK; Division of Infectious Diseases & Immunology, Indian Institute of Chemical Biology, 4, Raja S. C. Mallick Road, Jadavpur, Kolkata, 700032, West Bengal, India., Gunasekaran K; Center for Advanced studies in Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India., Vellaichamy E; Department of Biochemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India., Mohanakrishnan AK; Department of Organic Chemistry, School of Chemistry, University of Madras, Guindy Campus, Chennai, 600025, Tamil Nadu, India.
Jazyk: angličtina
Zdroj: ChemMedChem [ChemMedChem] 2019 Aug 06; Vol. 14 (15), pp. 1418-1430. Date of Electronic Publication: 2019 Jul 25.
DOI: 10.1002/cmdc.201900225
Abstrakt: 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 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.
(© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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