Thiopeptides are sulfur containing highly modified macrocyclic antibiotics with a central pyridine/tetrapyridine/dehydropiperidine ring with up to three thiazole substituents on positions 2, 3 and 6. Thiazole antibiotics with central pyridine nucleus have a macrocyclic loop connecting thiazole rings at position 2 and 3 described as ring A. In addition antibiotics with central tetrahydropyridine nucleus have a quinaldic acid macrocycle also connected to thiazole on position 2 described as ring B. We have demonstrated before that thiazole antibiotics thiostrepton and Siomycin A act as proteasome inhibitors in mammalian tumor cells. Here we decided to test whether other known thiazole antibiotics such as berninamycin, micrococcin P1 and P2, thiocillin and YM-266183 (lacking the quinaldic acid ring B) demonstrate this activity. We found that none of them act as proteasome inhibitors. Moreover, structural modification of thiostrepton to thiostrepton methyl ester (with open B ring) also did not demonstrate this activity. These data suggest that B ring of thiostrepton and Siomycin A that is absent in other thiazole antibiotics determines the proteasome inhibitory activity of these drugs.