Novel inhibitors of enkephalin-degrading enzymes. IV: Structure-activity relationships within the penicillins as enkephalinase inhibitors.
A range of penicillins have been examined as competitive reversible inhibitors of enkephalinase (neutral endopeptidase; EC 3.4.24.11). Carfecillin (Ki = 0.18 microM) was the most potent inhibitor in the series, whereas cloxacillin (27.5 microM), ampicillin (41.0 microM), nafcillin (58.7 microM) and carbenicillin (158 microM) had moderate potency and benzyl penicillin (885 microM), mezlocillin (473 microM) and azlocillin (556 microM) were weak inhibitors. Structure-activity relationships within the series have been rationalised from a consideration of molecular graphics analysis of the match between receptor binding groups with thiorphan as well as log P values.
Livingston
S J
SJ
Welsh School of Pharmacy, U.W.C.C., Cardiff, UK.
Smith
H J
HJ
Sewell
R D
RD
Ahmed
S
S
D003196:Computer Graphics; D008968:Molecular Conformation; D015394:Molecular Structure; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D010406:Penicillins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D010406:Penicillins; D015260:Neprilysin