Biomedical Engineering Reference
In-Depth Information
the German company Bayer in the mid 1970s [51]. Their screening aimed at
inhibitors of oligo- and polysaccharide degrading enzymes towards an orally
available drug contributing to Diabetes mellitus type II (non-insulin-depen-
dent) therapy [52,53].Enzyme inhibitors of this type were expected to reduce
food intake-caused blood glucose elevation by retarding degradation ofnutrient
oligo- and polysaccharides in the intestine.And in fact,acarbose can be applied
effectively when a diet alone fails to adequately control blood glucose levels.
Furthermore,it was shown that insulin dosing of patients suffering from Dia-
betes mellitus type I (insulin-dependent) can also take advantage of acarbose
because the exaggerated rise in blood glucose level after meals can be reduced.
Acarbose was first launched by Bayer in Germany under the trade name of
Glucobay in 1990.The pseudo-disaccharide moiety ofthe pseudo-tetrasaccharide
acarbose strongly inhibits the intestine located enzymes of the
-glucosidase
type by mimicking a disaccharide part of the starch molecule or related nutri-
ent polymers which functions as the natural substrate of the target enzymes.
The glucose moiety in acarbose is replaced by an unsaturated cyclohexitol
(C
7
N-unit),thus preventing degradation ofthe pseudo-tetrasaccharide as a com-
petitive enzyme inhibitor [54].
Bayer succeeded in reducing manufacturing costs of acarbose dramatically,
presumably mainly by increasing yields and shifting the fermentation process to
the desired homologous compound acarbose.Efforts to replace the fermentation
by chemical synthesis of a structurally simplified analog of the tetrasaccharide
failed.However,the profile oforal diabetes treatment by Bayer is actually comple-
mented by the monosaccharide miglitol, an additional
a
-glucosidase inhibitor
[55,56] which was synthesized starting from the naturally occurring 1-deoxyno-
jirimycin as a lead structure. Interestingly, 1-deoxynojirimycin can be isolated
from both,culture broths of streptomycetes and the bark of mulberry trees.
a
2.5
Anticancer Drugs
The example of the anticancer drug Taxol,introduced by Bristol-Myers Squibb
in 1993,demonstrates how to overcome the obstacles affecting the development
acarbose
miglitol
Fig. 3.
Antidiabetic drugs acarbose,and miglitol
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