Induction of lymphoproliferative popliteal lymph node reaction by hydantoin derivatives: structure-activity relationships.

We evaluated the ability of a series of 3-phenylhydantoin derivatives to induce a lymphoproliferative popliteal lymph node reaction in C57B1/6 mice. 5-Aryl-3-phenylhydantoins induced a significant lymphoproliferative reaction, whereas the 5-alkyl-substituted and the unsubstituted 3-phenylhydantoins did not. 5-Alkyl-3-phenylhydantoins were unable to induce a lymphoproliferative reaction, unlike the corresponding 5-alkyl-3-phenyl-2-thiohydantoins, which have been reported to induce a significant lymphoproliferative reaction in the same strain of mice. Based on these results, we suggest that, to induce a lymphoproliferative popliteal lymph node reaction, hydantoins have to bind covalently to proteins through the N-atoms if they are activated by electrophilic groups bound to the hydantoin ring. We also suggest that 2-thiohydantoins can bind through their S-atom, whereas hydantoins cannot do so through their O-atoms.

Synthesis and antibacterial activity of 7 beta-[3-(un)substituted-2-aminopropionamido]-3-vinylcephalosporin s and related compounds.

A series of new 7 beta-[3-(un)substituted-alanyl]-3-vinylcephalosporins and some related compounds, 4a-l is described. They incorporate residues of proteinogenic L-alpha-aminocarboxylic acids, their antimetabolites and enantiomers as well as a dipeptide in the 7 beta-acylamido side chain. The acylation of diphenyl-methyl 7-amino-3-vinyl-3-cephem-4-carboxylate (2: R2 = DPM) with various protected alpha-aminocarboxylic acids 1a-k and the dipeptide 1l is carried out using TBTU as coupling reagent. The compounds, except 4f, are active in vitro against S. aureus and S. lutea, but only 4a, 4k, and 4l inhibit some of the Gram-negative strains.