The role of combichem in antibiotic discovery

Combinatorial chemistry (combichem) has had a significant impact on the discovery of new antibiotics. Most of the successes have come from the use of small libraries to explore a specific pharmacophore. However, large diverse libraries are more appropriate when identifying hits by screening specific bacterial or fungal targets. Combichem has been used to optimize new azole and oxazolidinone leads. An entirely new class of antibiotics, inhibitors of bacterial peptidyl-deformylase, has been discovered by combining mechanism-based drug design and combichem. These compounds are active in vivo. The impact of combichem on discovery projects that aim to develop new antibiotics for the treatment of infectious diseases is discussed.