Fs. Nandel et al., CONFORMATIONAL STRUCTURE OF SOME BETA(1)-BLOCKERS, THEIR PARTITIONINGIN LIPID AND THE ROLE OF PARASUBSTITUENTS, Indian Journal of Biochemistry & Biophysics, 32(4), 1995, pp. 207-212
The conformational structure of beta(1)-blockers metoprolol, atenolol
and practolol has been investigated by PCILO method. The aminoalkanol
moiety adopts the same conformation in all these compounds. These beta
-antagonists differ only in the conformation adopted by the substituen
t para to the aminoalkanol moiety. The graphical representation of the
beta(1)-antagonists for the final conformation reveals that only in t
he S-form, three interacting sites, namely, aromatic moiety, the beta-
hydroxyl group and the -NH2+ groups of aminoalkanol moiety are availab
le for interactions with the receptor. The interaction of the aryloxy
oxygen of the beta-antagonists with water molecule has also been taken
into account. A linear relationship was obtained between log K (the p
artitioning of the beta-blocker in DMPC and also in octanol/water) and
the potencies of these beta(1)-antagonists. Possibly, the role of par
a substituent is to act as an anchor by partitioning in the lipid bila
yer so that the beta(1)-antagonist adopts the proper orientation for b
inding to the receptor.