Universität Bayreuth, Bayreuth.
Chem Biodivers. 2010 Dec;7(12):2830-45. doi: 10.1002/cbdv.201000179.
Fragments and synthetic precursors prepared en route to the macrocyclic 3-acyltetramic acids (=3-acyl-1,5-dihydro-4-hydroxy-2H-pyrrol-2-ones) aburatubolactam and macrocidin A, as well as other analogs with variance in the ring heteroatom (N, O, S), and the residues at N(1), C(3), and C(5) were tested for cytotoxic and antimicrobial effects. Anticancer activity against various tumor cell lines in vitro did not necessarily require an intact pyrrolidin-2,4-dione ring. An acyclic β-hydroxy-octatrienoyl amide precursor to aburatubolactam also exhibited distinct activity with an IC₅₀ (120 h) value of <2.5 μM. The length of 3-oligoenoyl residues had little influence on the anticancer activity, but 3-alka-oligoenoyl tetramic acids were far more efficacious than their 3-(4-methoxycinnamoyl) congeners. N-H-3-acyltetramic acids were generally more active than their N-Me or N-Boc analogs, unless further polar groups necessitated an increased lipophilicity for sufficient uptake. Tetronic and thiotetronic acids were far less antiproliferative in cancer cells when compared with identically substituted tetramic acids.
片段和合成前体，这些前体是制备大环 3-酰基四氢酸（=3-酰基-1,5-二氢-4-羟基-2H-吡咯-2-酮）aburatubolactam 和 macrocidin A 以及其他具有环杂原子（N、O、S）和 N(1)、C(3)和 C(5)残基变化的类似物的过程中制备的，测试了它们的细胞毒性和抗菌效果。体外对各种肿瘤细胞系的抗癌活性不一定需要完整的吡咯烷-2,4-二酮环。aburatubolactam 的无环 β-羟基-辛二烯酰酰胺前体也表现出明显的活性，IC₅₀（120 h）值<2.5 μM。3-寡烯酰残基的长度对抗癌活性影响不大，但 3-烷-寡烯酰四氢酸比它们的 3-（4-甲氧基肉桂酰）同系物更有效。N-H-3-酰基四氢酸通常比它们的 N-Me 或 N-Boc 类似物更活跃，除非需要进一步的极性基团来增加脂溶性以获得足够的摄取。与相同取代的四氢酸相比，四酮酸和硫代四酮酸在癌细胞中的增殖抑制作用要小得多。
