Optically active 1,3,4,4-tetrasubstituted β-lactams: Synthesis and evaluation as tumor cell growth inhibitors

The in vitro cytotoxicity assays of several enantiopure (3S,4S)- and (3R,4R)-1,3,4,4-tetrasubstituted β-lactams derived from amino acids have shown that the (3S,4S)-4-benzyl-1-p-methoxybenzyl-3-methyl-4-methoxycarbonyl derivative 2a, obtained from Phe, displays significant activity, which is comparable to that of the anticancer drug Doxorubicin against HT29 cell lines. Modifications at positions 1 and 4 of the β-lactam ring led to identify the Tyr(2,6-ClBz) analogu 26d with similar activity data to those of 2a. The synthesis and SAR of all these tetrasubstituted β-lactams are reported here.

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► We prepare enantiopure 1,3,4,4-tetrasubstituted beta-lactams.
► We evaluate these beta-lactams as inhibitors of tumor cell growth.
► A preliminary SAR study is reported.
► Some derivatives are equipotent to doxorubicin against HT29 colon cells.