Synthesis and structure–activity relationships of o-sulfonamido-arylhydrazides as inhibitors of ll-diaminopimelate aminotransferase (ll-DAP-AT)

Abstract

Recently, LL-diaminopimelate aminotransferase (LL-DAP-AT), a pyridoxal-5′-phosphate (PLP)-dependent enzyme, was reported to catalyze a key step in the biosynthesis of L-lysine in plants and Chlamydia. Previous screening of a 29 201-compound library against LL-DAP-AT identified an o-sulfonamidoarylhydrazide as a reversible inhibitor with IC₅₀ ∼ 5 μM. Structure–activity relationship (SAR) studies based on this lead compound identified key structural features essential for enzyme inhibition and led to slightly improved inhibitors. Preliminary studies on the mode of inhibition of LL-DAP-AT by this class of compounds are also reported.