Effect of some 4-alkyl-5-dimethylamino-1-phenyl-1-penten-3-one hydrochlorides and related compounds on respiration in mouse liver mitochondria.
5-Dimethylamino-1-phenyl-1-penten-3-one hydrochloride (1a) has high inhibiting properties in mitochondria isolated from mice liver. Substitution at the 4-methylene group of 1a by different alkyl substituents lead to compounds with wide variation in respiration-inhibiting properties. No correlations were found between either the Charton steric parameter (v), Taft inductive value (f*) or fragmental constant (f) of the substituents at position 4 of the Mannich bases with inhibition of respiration. However the biological results suggested two receptor sites were present in the mitochondria which may interact with the Mannich bases namely a common receptor for all compounds and in addition a narrow hydrophobic binding area which can accommodate a n-butyl or higher alkyl groups which are present in some of the compounds.
Dimmock
J R
JR
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
Hamon
N W
NW
De Gooijer
C A
CA
Grant
G F
GF
Jonnalagadda
S S
SS
Hancock
D S
DS
D000818:Animals; D001593:Benzyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D002855:Chromatography, Thin Layer; D004123:Dimethylamines / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010422:Pentanones / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D001593:Benzyl Compounds; D004123:Dimethylamines; D007659:Ketones; D010422:Pentanones