- Efficient Synthesis of Glaziovianin A Isoflavone Series from Dill and Parsley Extracts and Their in Vitro/in Vivo Antimitotic Activity
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A concise six-step protocol for the synthesis of isoflavone glaziovianin A (GVA) and its alkoxyphenyl derivatives 9 starting with readily available plant metabolites from dill and parsley seeds was developed. The reaction sequence involved an efficient conversion of the key intermediate epoxides 7 into the respective β-ketoaldehydes 8 followed by their Cu(I)-mediated cyclization into the target series 9. The biological activity of GVA and its derivatives was evaluated using a panel of seven human cancer cell lines and an in vivo sea urchin embryo assay. Both screening platforms confirmed the antimitotic effect of the parent GVA (9cg) and its alkoxy derivatives. Structure-activity relationship studies suggested that compounds 9cd and 9cf substituted with trimethoxy- and dillapiol-derived B-rings, respectively, were less active than the parent 9cg. Of the evaluated human cancer cell lines, the A375 melanoma cell line was the most sensitive to the tested molecules. Notably, the target compounds were not cytotoxic against human peripheral blood mononuclear cells up to 10 μM concentration. Phenotypic readouts from the sea urchin assay unequivocally suggest a direct microtubule-destabilizing effect of isoflavones 9cg, 9cd, and 9cf.
- Semenov, Victor V.,Tsyganov, Dmitry V.,Semenova, Marina N.,Chuprov-Netochin, Roman N.,Raihstat, Mikhail M.,Konyushkin, Leonid D.,Volynchuk, Polina B.,Marusich, Elena I.,Nazarenko, Vera V.,Leonov, Sergey V.,Kiselyov, Alex S.
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p. 1429 - 1438
(2016/06/09)
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- Synthesis of various kinds of isoflavones, isoflavanes, and biphenyl- ketones and their 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities
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Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10') were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1- diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12-54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E-I) and their biphenyl-ketone derivatives (10E-H) also showed a high activity (ED50=50=26-32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3'-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10') by metabolism or biotransformation.
- Goto, Hideyuki,Terao, Yoshiyasu,Akai, Shuji
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experimental part
p. 346 - 360
(2009/12/27)
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- Biotransformation of isoflavones by the larvae of the common cutworm (Spodoptera litura)
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Biotransformation of the 5,7,4′-trimethoxyisoflavone (1), 6,7,4′-trimethoxyisoflavone (2), and 7,4′-dimethoxyisoflavone (3) by insects, Spodoptera litura was investigated. Compound 1 was transformed to 5-hydroxy-7,4′-dimethoxyisoflavone (4), 7-hydroxy-5,4
- Takahashi, Koji,Araki, Hideo,Miyazawa, Mitsuo
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p. 719 - 721
(2007/10/03)
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