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Oxidized Juncuenin B Analogues with Increased Antiproliferative Activity on Human Adherent Cell Lines: Semisynthesis and Biological Evaluation

Bús, Csaba and Kulmány, Ágnes and Kúsz, Norbert and Gonda, Tímea and Zupkó, István and Mándi, Attila and Kurtán, Tibor and Tóth, Barbara and Hohmann, Judit and Hunyadi, Attila and Vasas, Andrea (2020) Oxidized Juncuenin B Analogues with Increased Antiproliferative Activity on Human Adherent Cell Lines: Semisynthesis and Biological Evaluation. JOURNAL OF NATURAL PRODUCTS, 83. pp. 3250-3261. ISSN 0163-3864

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Abstract

Phenanthrenes have become the subject of intensive research during the past decades because of their structural diversity and wide range of pharmacological activities. Earlier studies demonstrated that semisynthetic derivatization of these natural compounds could result in more active agents, and oxidative transformations are particularly promising in this regard. In our work, a natural phenanthrene, juncuenin B, was transformed by hypervalent iodine(III) reagents using a diversity-oriented approach. Eleven racemic semisynthetic compounds were produced, the majority containing an alkyl substituted p-quinol ring. Purification of the compounds was carried out by chromatographic techniques, and their structures were elucidated by 1D and 2D NMR spectroscopic methods. Stereoisomers of the bioactive derivatives were separated by chiral-phase HPLC and the absolute configurations of the active compounds, 2,6-dioxo-1,8a-dimethoxy-1,7-dimethyl-vinyl-9,10-dihydrophenanthrenes (1a−d), and 8a-ethoxy-1,7-dimethyl-6-oxo-8-vinyl-9,10-dihydrophenanthrene-2-ols (7a,b) were determined by ECD measurements and TDDFT-ECD calculations. The antiproliferative activities of the compounds were tested on different (MCF-7, T47D, HeLa, SiHa, C33A, A2780) human gynecological cancer cell lines. Compounds 1a−d, 4a, 6a, and 7a possessed higher activity than juncuenin B on several tumor cell lines. The structure−activity relationship studies suggested that the p-quinol (2,5-cyclohexadien-4-hydroxy-1-one) moiety has a considerable effect on the antiproliferative properties, and substantial differences could be identified in the activities of the stereoisomers.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD01 Analytical chemistry / analitikai kémia
Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Q Science / természettudomány > QK Botany / növénytan
Depositing User: Mándi Attila
Date Deposited: 19 Sep 2021 15:22
Last Modified: 03 Apr 2023 07:21
URI: http://real.mtak.hu/id/eprint/129772

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