Synthesis and evaluation of benzoylbenzofurans and isoflavone derivatives as sirtuin 1 inhibitors with antiproliferative effects on cancer cells.

Autor: Selepe MA; Department of Chemistry, University of Pretoria, Lynnwood Rd, Hatfield, Pretoria 0002, South Africa. Electronic address: mamoalosi.selepe@up.ac.za., Kunyane P; Department of Chemistry, University of Pretoria, Lynnwood Rd, Hatfield, Pretoria 0002, South Africa., Seboletswe P; School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000, South Africa., Nair S; Radiation Biophysics Division, Separated Sector Cyclotron Laboratory, NRF-iThemba LABS, Cape Town 7131, South Africa., Cele N; School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000, South Africa., Engelbrecht M; Radiation Biophysics Division, Separated Sector Cyclotron Laboratory, NRF-iThemba LABS, Cape Town 7131, South Africa., Joubert DF; Department of Physiology, University of Pretoria, Lynnwood Rd, Hatfield, Pretoria 0002, South Africa., Vandevoorde C; Radiation Biophysics Division, Separated Sector Cyclotron Laboratory, NRF-iThemba LABS, Cape Town 7131, South Africa., Singh P; School of Chemistry and Physics, University of KwaZulu-Natal, P/Bag X54001, Westville, Durban 4000, South Africa. Electronic address: Singhp4@ukzn.ac.za., Sonopo MS; Radiochemistry, South African Nuclear Energy Corporation Ltd, Pelindaba, Brits 0240, South Africa. Electronic address: Molahlehi.Sonopo@necsa.co.za.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2022 Nov; Vol. 128, pp. 106101. Date of Electronic Publication: 2022 Aug 17.
DOI: 10.1016/j.bioorg.2022.106101
Abstrakt: Isoflavone derivatives were prepared from benzoylbenzofuran precursors. The synthesized compounds were analyzed by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, as well as high-resolution mass spectrometry (HRMS) to confirm their structures. The benzoylbenzofuran and isoflavone analogues were evaluated for inhibition of sirtuin 1 (SIRT1) and cell proliferation in MDA-MB-231 triple-negative breast cancer (TNBC) cells. Several isoflavone and benzoylbenzofuran derivatives exhibited potent antiproliferative effects against the MDA-MB-231 cancer cell line. Most of the isoflavone derivatives attenuated SIRT1 activity to below 50%. The most active compounds were the isoflavone quinones 38, 39, and 40, at IC 50 values of 5.58 ± 0.373, 1.62 ± 0.0720, and 7.24 ± 0.823 μM, respectively. Importantly, the most active compound, 6-methoxy-4',6'-dimethylisoflavone-2',5'-quinone (39) displayed SIRT1 inhibitory activity comparable to that of the reference compound, suramin. The in silico docking simulations in the active site of SIRT1 further substantiated the experimental results and explored the binding orientations of potent compounds in the active site of the target.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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