Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8, H-1111, Budapest, Hungary; Gedeon Richter Plc., Gyömrői út 19-21, H-1103, Budapest, Hungary.
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Budafoki út 8, H-1111, Budapest, Hungary.
Eur J Med Chem. 2019 Jul 1;173:76-89. doi: 10.1016/j.ejmech.2019.04.010. Epub 2019 Apr 8.
A series of (±)-trans-dihydronarciclasine and (±)-trans-dihydrolycoricidine derivatives with variously substituted ring A was synthesised and evaluated for their antiproliferative activity against 60 human tumour cell lines (NCI60), representing leukemia, melanoma, and cancers of the lung, colon, brain, ovary, breast, prostate, as well as kidney in vitro. Among the 13 alkaloids screened, (±)-trans-dihydronarciclasine showed the highest potency as a cytotoxic molecule. A structure-activity relationship (SAR) study indicated that the presence of a hydroxy group at position 7 and a rigid, 1,3-benzodioxole scaffold were essential for the antiproliferative activity.
一系列具有不同取代基的环 A 的（±）-反式二氢纳曲酮和（±）-反式二氢石蒜碱衍生物被合成，并在体外针对 60 个人类肿瘤细胞系（NCI60）进行了抗增殖活性评估，这些细胞系代表白血病、黑色素瘤以及肺癌、结肠癌、脑癌、卵巢癌、乳腺癌、前列腺癌和肾癌。在所筛选的 13 种生物碱中，（±）-反式二氢纳曲酮显示出作为细胞毒性分子的最高效力。构效关系（SAR）研究表明，位置 7 上的羟基和刚性的 1,3-苯并二恶唑骨架的存在对于抗增殖活性是必需的。
