Li Wei, Li Xueli, Liu Manhui, Wang Qiuan
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Changsha, P. R. China.
Arch Pharm (Weinheim). 2017 Jul;350(7). doi: 10.1002/ardp.201700044. Epub 2017 Jun 12.
Two series of 12 novel thioxoflavones Mannich base derivatives 5a-f and 6a-f were synthesized via Mannich reaction of 4',7-dimethoxy-5-hydroxyflavothione (3) or 3',4',7-trimethoxy-5-hydroxyflavothione (4) with appropriate aliphatic amines or alicyclic amines and formaldehyde. Thioxoflavones 3 and 4 were prepared from 4',7-dimethoxy-5-hydroxyflavone (1) and 3',4',7-trimethoxy-5-hydroxyflavone (2) with Lawesson's reagent, respectively. Their antiproliferative activities in vitro were evaluated on a panel of three human cell lines (HeLa, HCC1954, and SK-OV-3) by CCK-8 assay. The results showed that most of the thioxoflavones and their Mannich base derivatives exhibited potential antiproliferative activities on the tested cancer cell lines, with IC values ranging from 9.16 to 55.50 μM. In particular, thioxoflavone 4 and the thioxoflavone Mannich base derivatives 5a and 5d showed the best antiproliferative activity on all three human cancer cell lines; they are promising candidates worthy of further development. The structures of all synthesized compounds were confirmed by H NMR, C NMR, IR, and MS techniques.
通过4',7-二甲氧基-5-羟基硫代黄酮（3）或3',4',7-三甲氧基-5-羟基硫代黄酮（4）与合适的脂肪族胺或脂环族胺及甲醛的曼尼希反应，合成了两个系列的12种新型硫代黄酮曼尼希碱衍生物5a-f和6a-f。硫代黄酮3和4分别由4',7-二甲氧基-5-羟基黄酮（1）和3',4',7-三甲氧基-5-羟基黄酮（2）与劳森试剂制备。通过CCK-8法在三种人类细胞系（HeLa、HCC1954和SK-OV-3）上评估了它们的体外抗增殖活性。结果表明，大多数硫代黄酮及其曼尼希碱衍生物在测试的癌细胞系上表现出潜在的抗增殖活性，IC值范围为9.16至55.50 μM。特别是，硫代黄酮4以及硫代黄酮曼尼希碱衍生物5a和5d在所有三种人类癌细胞系上均表现出最佳的抗增殖活性；它们是值得进一步开发的有前景的候选物。所有合成化合物的结构均通过1H NMR、13C NMR、IR和MS技术得以确证。
