Dichloroacetate synergizes Alpha Lipoic Acid
There is a U.S. Patent showing that alpha lipoic acid works well with dichloroacetate.
The section below is from United States Patent 6331559, from 2001 and United States Patent 6951887 from 2005.
PLEASE do not attempt to contact the owners of this patent. We have already spoken to them and they are very private about their work. Please respect that privacy and do not bother them!! They don't like it and they will get upset with us. You need to know there is synergism of DCA and alpha lipoic acid.
One likely mechanism of action of the blocked lipoate (this is the base of lipoic acid) derivatives that are the object of this invention is that they inhibit PDC specifically in cancer cells resulting in loss of mitochondrial membrane polarization and consequent induction of apoptosis in cancer cells. It is anticipated that blocked lipoate derivatives might interact synergistically with other agents that either inhibit mitochondrial energy metabolism and/or induce apoptosis in some other fashion.
This was tested in this Example with dichloroacetate (henceforth abbreviated DCA)(8). This compound is a pyruvate analog. As such, one of its effects is expected to be competitive inhibition of PDC. It was found that this compound interacts synergistically with blocked lipoate derivatives as expected. A relevant experimental observation is as follows.
HeLa cells were plated at moderate densities and allowed to attach and grow for ca. 24 hours in a series of wells in a multi-well tissue culture plate. To individual wells of the first subset (control) were added bis-acetyl lipoate, mono-acetyl lipoate or bis-benzoyl lipoate--each at ca. twofold above the threshold killing dose (EXAMPLE 11). To an equivalent (experimental) subset of wells were added these same compounds at the same dose together with the simultaneous addition of DCA to 5 mM final concentration. We find that the cells of the experimental subset are killed approximately twice as rapidly as in the control subset.
This was a striking effect. At 24 hours post treatment the experimental group was almost entirely killed, whereas a similar level of nearly complete killing was not seen until ca. 48 hours in the control subset.
Based on experimental observations of this sort, it is likely that these lipoate derivatives of this invention will interact synergistically with other metabolic inhibitors and/or other chemotherapeutic agents to kill cancer cells more efficiently. Indeed, one effective clinical application of the novel compounds that are the object of this invention may be in concert with other agents. "