Laboratory of Bio-organic Chemistry, Tokyo Denki University, Hatoyama, Japan;
Laboratory of Bio-organic Chemistry, Tokyo Denki University, Hatoyama, Japan.
Anticancer Res. 2024 Sep;44(9):3849-3855. doi: 10.21873/anticanres.17211.
BACKGROUND/AIM: Flavonoids represent a privileged scaffold for medicinal chemists because of versatile synthetic transformation into a large variety of functionalized derivatives and are known to exhibit a variety of biological activities and their potential as anticancer agents is being investigated. As part of our continuing investigation of flavonoid derivatives as potential anticancer substances, a series of 3-methylflavones were synthesized, and their antiproliferative activity was evaluated in leukemic HL60 cells.
3-Methylflavones were directly synthesized from the 2-propionylphenyl benzoate esters prepared from combination of 2'-hydroxypropiophenone with appropriate benzoic acid derivatives by the modified conditions of Yamaguchi esterification. The synthesized 3-methylflavones were tested in leukemic HL60 cells to assess their antiproliferative activity.
Among the synthesized compounds, 3,3'-dimethylflavone showed the most potent activity (IC=76 μM), although the introduction of C3-methyl group in flavone tended to reduce the biological activity.
Synthesis of a series of 3-methylflavones as anticancer agents conducted and their antiproliferative activity evaluated. Although the one carbon homologation at C3 position of flavones weakened their activity, atropisomerism can be highlighted as the remarkable phenomenon of 3-methylflavones.
背景/目的：黄酮类化合物因其在多种功能化衍生物中的多功能合成转化而成为药物化学家的重要骨架，已知其具有多种生物活性，并且它们作为抗癌剂的潜力正在被研究。作为我们对黄酮类衍生物作为潜在抗癌物质的持续研究的一部分，合成了一系列 3-甲基黄酮，并在白血病 HL60 细胞中评估了它们的抗增殖活性。
3-甲基黄酮直接由 2'-羟基丙基苯甲酰基酯合成，该酯由 2'-羟基丙基苯甲酮与适当的苯甲酸衍生物组合，通过 Yamaguchi 酯化的改良条件制备。将合成的 3-甲基黄酮在白血病 HL60 细胞中进行测试，以评估其抗增殖活性。
在所合成的化合物中，3,3'-二甲基黄酮显示出最强的活性（IC=76 μM），尽管在黄酮中引入 C3-甲基基团往往会降低生物活性。
进行了一系列作为抗癌剂的 3-甲基黄酮的合成，并评估了它们的抗增殖活性。尽管在黄酮的 C3 位置的一个碳原子同系化削弱了它们的活性，但手性异构现象可以被突出为 3-甲基黄酮的显著现象。
