Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1111, Budapest, Gellért tér 4., Hungary.
Spectroscopic Research Department, Gedeon Richter Plc., H-1475, Budapest 10, P.O. Box 27, Hungary.
Chem Biodivers. 2022 Jan;19(1):e202100725. doi: 10.1002/cbdv.202100725. Epub 2021 Dec 7.
Vinca alkaloids are well-known microtubule targeting agents, which are used against some types of cancer. Vindoline is one of the monomeric Vinca alkaloids which does not have anti-tumor effect, although its derivatives have serious impact on the field of these indole alkaloids. Chrysin is a secondary plant metabolite, which has broad-spectrum biological activity, among others anticancer activity. Chrysin had shown synergic effect with several antiproliferative compounds (e. g., doxorubicin, cisplatin and ciglitazone), therefore, we attempted the synthesis of a novel vindoline-chrysin hybrid molecule. However, in the first case a diphenylamine structure was isolated. The mechanism of the unexpected reaction was studied, and then the originally targeted hybrid was synthesized by a reverse route coupling. A further hybrid was produced using a different site of the molecule. The antitumor activities were determined against 60 human tumor cell lines (NCI60), where the aimed hybrid showed low micromolar GI values on most of the cell lines.
长春生物碱是众所周知的微管靶向剂，用于治疗某些类型的癌症。长春质碱是单体长春生物碱之一，虽然它的衍生物对这些吲哚生物碱领域有严重的影响，但它没有抗肿瘤作用。白杨素是一种次生植物代谢物，具有广谱的生物活性，包括抗癌活性。白杨素与几种抗增殖化合物（如阿霉素、顺铂和噻唑烷二酮）表现出协同作用，因此，我们尝试合成一种新型长春质碱-白杨素杂合分子。然而，在第一种情况下，分离出了二苯胺结构。研究了意外反应的机制，然后通过反向偶联合成了最初靶向的杂合分子。使用分子的不同部位合成了另一种杂合分子。对 60 个人类肿瘤细胞系（NCI60）进行了抗肿瘤活性测定，其中目标杂合分子在大多数细胞系中表现出低微摩尔 GI 值。
