8.8.1.7 Zinc
Zinc is used for a variety of indications. Zinc acetate (8.102) or, rarely, zinc sulfate (8.103)
have been used orally to treat Wilson’s disease, a recessively inherited disorder of copper
metabolism, characterized by brain and liver dysfunction arising from excessive deposits
of copper. Zinc pyrithione (8.104) is used in shampoos to treat seborrhea. Zinc propionate
(8.105) and zinc caprylate (8.106) have been used as topical antifungal agents.
8.8.1.8 Other Metals
Of historical interest, arsenical antibiotics (8.107) were once used to treat syphilis and
mercurial diuretics (8.108) were once used to treat edema and to promote water excre-
tion. Due to their high toxicity, neither is currently used.
8.8.2 Inorganic Substances as Drug ReceptorsThere are several structures in which inorganic substances may act as receptors for drugs.
8.8.2.1 Endogenous Organo-Metallic Macromolecules as Drug Receptors
Metallo-Enzymes.These are enzymes that have a metal atom at their active site. This
atom may play a role as a point of contact with the drug pharmacophore. A good
example of this is provided by the discovery of angiotensin-converting enzyme (ACE)
inhibitors for the treatment of high blood pressure. The ACE enzyme contains a zinc
atom. Drug design of enzyme inhibitors, such as captopril, has targeted the zinc through
the binding process.
Zinc Fingers. A zinc finger is part of a protein that binds to DNA, forming a com-
plex stabilized in part by the presence of a zinc cation. A zinc finger typically has two
β-sheets, each with a cysteine amino acid residue, and an α-helix with two histidine
residues. These four amino acids form the chelating moiety that holds the zinc ion.
Since zinc fingers are proteins that bind to DNA, their manipulation has the capacity to
influence genome expression. Zinc fingers have been considered as targets for breast
cancer therapy development.
8.8.2.2 Inorganic Salts as Drug Receptors
About 98% of the 1.5 kg of calcium and 85% of the 1 kg of phosphorus in the human
adult are found in bone. Bone is composed of two distinct tissue structures: cortical
ENDOGENOUS MACROMOLECULES 535