What is Sodium
Dichloroacetate?
CHCl2COOH
| Dichloroacetic acid |
 |
 |
IUPAC name[hide]
Dichloroacetic acid
|
Other names[hide]
Dichloroethanoic acid
|
| Identifiers |
| CAS number |
79-43-6  Y |
| PubChem |
6597 |
| ChemSpider |
10771217 Y |
| UNII |
9LSH52S3LQ Y |
| MeSH |
Dichloroacetate |
| RTECS number |
AG6125000 |
|
|
InChI=1S/C2H2Cl2O2/c3-1(4)2(5)6/h1H,(H,5,6) Y
Key: JXTHNDFMNIQAHM-UHFFFAOYSA-N Y
InChI=1/C2H2Cl2O2/c3-1(4)2(5)6/h1H,(H,5,6)
Key: JXTHNDFMNIQAHM-UHFFFAOYAK
|
| Properties |
| Molecular formula |
C2H2Cl2O2 |
| Molar mass |
128.94 g/mol |
| Appearance |
colorless liquid |
| Density |
1.5634 g/cm3 (20 °C) |
| Melting point |
9-11 °C |
| Boiling point |
194 °C |
| Solubility in water |
miscible |
| Solubility |
miscible with ethanol, diethyl ether |
| Acidity (pKa) |
1.25 |
| Thermochemistry |
Std enthalpy of
formation ΔfHo298 |
-496.3 kJ·mol-1 |
| Hazards |
| MSDS |
MSDS (jtbaker) |
| R-phrases |
R35,
R50 |
| S-phrases |
(S1/2),
S26,
S45,
S61 |
| Related compounds |
| Related chloroacetic acids |
Chloroacetic acid
Trichloroacetic acid |
| Related compounds |
Acetic acid
Difluoroacetic acid
Dibromoacetic acid |
Y(what is this?) (verify)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa) |
| Infobox references |
|
Dichloroacetic acid, often abbreviated DCA, is the chemical
compound with formula
CHCl2COOH.
It is an acid, an analogue of acetic acid in which two of
the three hydrogen atoms of the methyl group have been
replaced by chlorine atoms. The salts and esters of
dichloroacetic acid are called dichloroacetates. Salts of
DCA are used as drugs since they inhibit the enzyme pyruvate
dehydrogenase kinase.
Early reports of its activity against brain cancer cells led
patients to treat themselves with DCA, which is commercially
available in non-pharmaceutical and pharmaceutical grade. A
phase 1 study in 5 patients concluded that DCA was safe, but
wasn't designed to establish effectiveness. Phase two, human
trials, have now been completed and are elaborated on below.
Chemistry and occurrence
The chemistry of dichloroacetic acid is typical for
halogenated organic acids. It is a member of the
chloroacetic acids family. The dichloroacetate ion is
produced when dissolved in water. As an acid with a pKa of
1.48, pure dichloroacetic acid is very corrosive and
extremely destructive to tissues of the mucous membranes and
upper respiratory tract.
DCA does not occur in nature. It is a trace product of the
chlorination of drinking water and is produced by the
metabolism of various chlorine-containing drugs or
chemicals. It is typically prepared by the reduction of
trichloroacetic acid.
Therapeutic use
Owing to the highly corrosive action of the acid, only the
salts of dichloroacetic acid are used therapeutically,
including its sodium and potassium salts, sodium
dichloroacetate and potassium dichloroacetate.
Lactic acidosis
The dichloroacetate ion stimulates the activity of the
enzyme pyruvate dehydrogenase by inhibiting the enzyme
pyruvate dehydrogenase kinase. Thus, it decreases lactate
production by shifting the metabolism of pyruvate from
glycolysis towards oxidation in the mitochondria. This
property has led to trials of DCA for the treatment of
lactic acidosis in humans.
A randomized controlled trial in children with congenital
lactic acidosis found that while DCA was well tolerated, it
was ineffective in improving clinical outcomes. A separate
trial of DCA in children with MELAS (a syndrome of
inadequate mitochondrial function, leading to lactic
acidosis) was halted early, as all 15 of the children
receiving DCA experienced significant nerve toxicity without
any evidence of benefit from the medication. A randomized
controlled trial of DCA in adults with lactic acidosis found
that while DCA lowered blood lactate levels, it had no
clinical benefit and did not improve hemodynamics or
survival.
Thus, while early case reports and pre-clinical data
suggested that DCA might be effective for lactic acidosis,
subsequent controlled trials have found no clinical benefit
of DCA in this setting. In addition, clinical trial subjects
were incapable of continuing on DCA as a study medication
owing to progressive toxicities.
Cancer applications
Cancer cells generally use glycolysis rather than
respiration (oxidative phosphorylation) for energy (the
Warburg effect), as a result of hypoxia that exists in
tumors and damaged mitochondria. Usually dangerously damaged
cells kill themselves via apoptosis, a mechanism of
self-destruction that involves mitochondria, but this
mechanism fails in cancer cells.
A phase one study published in January 2007 by researchers
at the University of Alberta, testing DCA on in vitro human
cancer cell lines and a rat model, found that DCA restored
mitochondrial function, thus restoring apoptosis, killing
cancer cells in vitro, and shrinking the tumors in the rats.
These results received extensive media attention, beginning
with an article in New Scientist titled "Cheap, ‘safe’ drug
kills most cancers". Subsequently, the American Cancer
Society and other medical organizations have received a
large volume of public interest and questions regarding DCA.
Reports have since pointed out that although the study
results are promising, no formal clinical trials in humans
with cancer have yet been conducted in the USA and are not
yet final in Canada, emphasizing the need for caution in
interpreting the preliminary results.
