I. Rozas et M. Martin, EFFECT OF BRANCHING IN 4-ALKYLPYRAZOLES ON LIVER ALCOHOL-DEHYDROGENASE INHIBITION - A SHAPE-ANALYSIS STUDY, Journal of molecular graphics, 12(4), 1994, pp. 267-274
Shape analysis methodology is applied to the study of 4-alkylpyrazoles
which are known inhibitors of liver alcohol dehydrogenase. Elongation
of the alkyl chain increases the inhibitory power, whereas branching
of the chain diminishes the activity. These two counterpoised effects
are studied simultaneously in a selected set of 4-alkylpyrazoles. A sy
stematic conformational analysis followed by topological characterizat
ion of the van der Waals surfaces of all the local minima restricts th
e conformational space to potential bioactive structures. The analysis
of the interrelation between the molecular electrostatic potential an
d van der Waals surfaces provides certain shape codes characteristic o
f each 4-alkylpyrazole. In both topological analyses (van der Waals su
rfaces and molecular electrostatic potential-van der Waals surface int
errelations) graphical representations and analytical methods were use
d. A good correlation between the shape codes and the inhibitory activ
ity is found for the linear derivatives. For branched pyrazoles, a ten
dency in their inhibitory power is predicted. Isopentylpyrazole is sug
gested to have the same inhibitory profile as 4-butylpyrazole, the lin
ear derivative with one less carbon atom.