Дихлорқабықша қышқылы: қасиеттері, қолданылуы және зерттеулер

chembox
| Watchedfields = changed
| verifiedrevid = 443301790
| ImageFileL1 = Dichloroacetic acid 2D skeletal. png
| ImageFileR1 = Dichloroacetic acid 3D vdW. png
| PIN = Dichloroacetic acid
| OtherNames = Dichloroethanoic acid, bichloroacetic acid, DCA, BCA, dichloracetic acid, bichloracetic acid
|Section1=
|Section2=Chembox Properties
| C=2 | H=2 | Cl=2 | O=2
| Appearance = Colorless liquid
| Density = 1.5634 g/cm3 (20 °C)
| MeltingPtC = 9 to 11
| MeltingPt notes =
| BoilingPtC = 194
| BoilingPt notes =
| Solubility = miscible
| SolubleOther = miscible with ethanol, diethyl ether pure dichloroacetic acid is classed as a strong organic acid; it is very corrosive and extremely destructive to tissues of the mucous membranes and upper respiratory tract via inhalation.

DCA has been shown to occur in nature in at least one seaweed, Asparagopsis taxiformis and also in the mushroom Russula nigricans. It is a trace product of the chlorination of drinking water and is produced by the metabolism of various chlorine containing drugs or chemicals. DCA is typically prepared by the reduction of trichloroacetic acid (TCA). DCA is prepared from chloral hydrate also by the reaction with calcium carbonate and sodium cyanide in water followed by acidifying with hydrochloric acid. It can also be made by passing acetylene through solutions of hypochlorous acid. As a laboratory reagent, both DCA and TCA are used as precipitants to prompt macromolecules such as proteins to precipitate out of solution.

Salts of DCA have been studied as potential drugs because they inhibit the enzyme pyruvate dehydrogenase kinase. Although preliminary studies found that DCA can slow the growth of certain tumors in animal studies and in vitro studies, as of 2012 insufficient evidence supported the use of DCA for cancer treatment.

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.

In 2007 reports emerged in the press and via the Internet that Evangelos Michelakis and coworkers at the University of Alberta had found that dichloroacetic acid, or rather its sodium salt sodium dichloroacetate, reduced tumors in rats and killed cancer cells in vitro. A story in New Scientist sparked "unprecedented interest among readers", as it spoke of "a cheap and simple drug" that was "known to be relatively safe" and could kill most cancers. An accompanying editorial pointed out that no drug company would be interested in getting the compound approved as a cancer treatment because it is unpatentable. The magazine later published an article emphasizing the dangers involved, such as damage to nerves. The US Food and Drug Administration began enforcing a law that prohibits the sale of substances with the suggestion that they are cancer treatments unless they have been approved by the FDA. The American Cancer Society in 2012 stated that "available evidence does not support the use of DCA for cancer treatment at this time." One problem with attempting this is obtaining the chemical. One fraudster was sentenced to 33 months in prison for selling a white powder containing starch, but no DCA, to people with cancer. The only monitored in vivo dosage of five human patients with glioblastoma with DCA was not designed to test its efficacy against their cancer. This study was rather to see whether it could be given at a specific dosage safely without causing side effects (e. g. neuropathy). All five patients were receiving other treatments during the study. Observations in vitro and of tumours extracted from those five patients suggest that DCA might act against cancer cells by depolarising abnormal mitochondria found in glioblastoma cancer cells – allowing the mitochondria to induce apoptosis (cell death) of the malignant cells. A 2016 case report discusses and reviews the potential application of DCA in central nervous system malignancies. A 2018 study found that DCA could trigger a metabolic switch from glycolysis (the Warburg effect) to mitochondrial OXPHOS and increase reactive oxygen stress affecting tumor cells. These effects were not observed in non tumor cells.

Neuropathy has been a problem in some clinical trials with DCA causing them to be effectively halted, The mechanism of DCA induced neuropathy is not well understood. On the one hand in vitro work with nerves has suggested a mechanism for the neuropathic effect of DCA; with DCA showing a dose and exposure dependent demyelination of nerves (stripping of the nerve 'sheath'), which demyelination was partially reversible over time, following washout of DCA. On the other hand, the 2008 review in BJC There is also evidence that DCA improves metabolism by NADH production stimulation, but may lead to a depletion of NADH in normoxia.