Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.
TriMen Chemicals, Piłsudskiego 141, 92-318 Łódź, Poland.
Molecules. 2020 Apr 14;25(8):1789. doi: 10.3390/molecules25081789.
Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.
秋水仙碱是一种具有强抗增殖活性的知名化合物，但由于其毒性，在化疗中的应用受到限制。为了创造更有效的抗癌药物，通过同时在 C7（酰胺和磺酰胺）和 C10（甲氨基）位置进行修饰，获得了一系列新型秋水仙碱衍生物，并通过光谱方法进行了表征。所有合成的化合物都已在体外进行测试，以评估它们对 A549、MCF-7、LoVo、LoVo/DX 和 BALB/3T3 细胞系的细胞毒性。此外，还使用涉及秋水仙碱衍生物与β-微管蛋白对接的计算方法研究了研究化合物的活性。大多数获得的衍生物对测试的癌细胞系的细胞毒性均高于秋水仙碱、阿霉素或顺铂。此外，对获得的化合物进行分子建模研究表明，它们可能以多种方式结合到微管蛋白的秋水仙碱结合位点。
