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Structure–Activity Relationships of Precursors and Analogs of Natural 3‐Enoyl‐tetramic Acids
Author(s) -
Barnickel Bertram,
Bayliffe Frances,
Diestel Randi,
Kempf Karl,
Laschat Sabine,
Pachali Steffen,
Sasse Florenz,
Schlenk Andrea,
Schobert Rainer
Publication year - 2010
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201000179
Subject(s) - chemistry , lipophilicity , stereochemistry , amide , heteroatom , ring (chemistry) , amino acid , biochemistry , organic chemistry
Abstract Fragments and synthetic precursors prepared en route to the macrocyclic 3‐acyltetramic acids (=3‐acyl‐1,5‐dihydro‐4‐hydroxy‐2 H ‐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 IC 50 (120 h) value of <2.5 μ M . 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.