Synthesis and biological evaluation of naphthoquinone analogs as a novel class of proteasome inhibitors

PI-083 was identified as a chymotrypsin-like reversible proteasome inhibitor. A series of novel naphthoquinone derivatives were synthesized and evaluated for proteasome chymotrypsin-like activity. The SAR data showed pyridyl sulfonamide moiety in PI-083 is crucial for activity. Other heterocyclic moieties such as thiazole, oxazole and thiadiazole moieties are tolerated.