Chemistry Reference
In-Depth Information
In studying the serum silicon levels in apparently healthy individuals, Bissé et al.
noted differences between men and women that were significantly age dependent
[
55
]. In study populations that were 18-44 years of age women were found to have
a higher serum silicon level than men up to a maximum difference of 21 % which
was observed in individuals in the 30-44 years old age group. This study noted that
as men age from 18-59 years of age their serum silicon levels increase to a median
of 9.7-10.2 μmol/L. As women aged from 18-44 years of age their serum silicon
levels were shown to increase with a median range of 10.0-11.1 μmol/L. Over the
age of 60 women exhibited a decrease in their serum silicon concentrations of ap-
proximately 28 %. Depending on the analytical technique employed, other studies
have reported human serum and plasma silicon values ranging from 0.60 ± 0.36 to
21.5 ± 4.5 μmol/L [
59
-
70
] Brown reported that one area where the human body
tends to exhibit a decrease in silicon content is the skin [
71
]. Based on the observed
serum silicon levels in women it has been speculated that serum silicon levels cor-
relate with hormone levels as women in age groups that had the highest hormonal
activity also demonstrated the highest level of silicon concentrations [
55
,
72
].
1.3.2.2
Silicon in Medicine
1.3.2.2.1
Silicon-Containing Molecules with Medicinal Applications
A number of silicon-containing molecules have been synthesized in the last 30 years
or so with designs on somehow influencing animal physiology. The use of silicon
containing small molecules as bioactive compounds has garnered a great deal of
attention because in many cases the differences in the chemical properties of the
silicon compounds demonstrate enhanced potency and improved pharmocological
characteristics in comparison to the carbon analogues (Chap. 8) [
73
].
A number of silicon-containing drug compounds have been inspired by purely
organic drugs or as variants of existing organic-based drug compounds (Fig.
1.4
)
[
73
-
89
].
Cyclooxygenase-2 (COX-2) has been implicated in a number of pathological con-
ditions. Non-steroidal anti-inflammatory drugs (NSAIDs) have demonstrated effec-
tiveness at inhibiting COX, however, in addition to inhibiting COX-2 NSAIDs also
inhibit COX-1 which is involved in renal and gastrointestinal protection and may
cause a number of drug-related side effects [
90
]. As a result finding a selective COX-
2 inhibitor has garnered a great deal of attention. Compound
1
is a lipophilic silicon-
based analogue of indomethacin and has proven to selective for inhibiting human
COX-2 in recombinant cell lines [
74
,
80
]. The derivative of
1
where R
1
= R
2
= R
3
= Me
and
n
= 3 demonstrated antiproliferative activity against pancreatic carcinoma cells
with an IC
50
= 6.0 μM compared to an IC
50
> 100 μM for indomethacin itself.
Phthalocyanine 4 (Pc 4)
2
developed by Kenney et al. represents a potential
tool in the photodynamic therapy of cancer by employing a photosensitizer (in this
case
2
), light and oxygen to eradicate cancer cells [
77
,
82
-
84
]. Pc 4
2
has demon-
strated encouraging anti-cancer activity both
in vitro
and
in vivo
to the point where
the molecule has entered clinical trials [
83
]. However, given the hydrophobicity
