Benzylpenicillin penicillin inhibitors

A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase [119,120]. Carfecillin K = 0.18 M) was the most potent inhibitor in the series, whereas cloxacillin (Aj = 27.5 //M), ampicillin (A = 41 //M), nafcillin (A = 59 //M) and carbenicillin (Aj =158 juM) had moderate potency and benzylpenicillin (A = 885 jUM), mezlocillin (Aj = 437 juM) and azlocillin (Kj = 556 //M) were weak inhibitors. Structure-activity relationships within the series have been rationalized... 

Early workers [29] found that, like benzylpenicillin, vancomycin, ristocetin and bacitracin, novobiocin caused an excessive accumulation of cell wall precursor, uridine diphosphate-7V-acetylmuramic acid-L-alanine-D-glutamic acid-L-lysine-D-alanine-D-alanine (UDP-MurNAc-L-ala-D-glu-L-lys-D-ala-D-ala) in Staph, aureus and it was thus considered that novobiocin was a specific inhibitor of peptidoglycan synthesis with an effect similar to that of penicillin. However, subsequent studies led to the withdrawal of this hypothesis [26], since novobiocin caused the accumulation of other precursor-type compounds and also strongly inhibited both nucleic acid and protein synthesis in this organism. Thus, accumulation of particular precursors does not necessarily reflect the site of action of an antibacterial agent [30]. 

---