Gallium maltolate is a
coordination complex consisting of a trivalent
gallium cation coordinated to three
maltolateligands. The compound is a potential therapeutic agent for cancer, infectious disease, and inflammatory disease.[1][2][3][4] A cosmetic skin cream containing gallium maltolate is marketed under the name Gallixa. It is a colorless solid with significant solubility in both water and lipids (
octanol-water partition coefficient = 0.41).[1]
Mechanism of action
Gallium maltolate delivers gallium with higher oral
bioavailability than that of gallium salts such as gallium nitrate and
gallium trichloride.[1]In vitro studies have found gallium to be antiproliferative due primarily to its ability to mimic ferric iron (Fe3+). Ferric iron is essential for
DNA synthesis, as it is present in the active site of the enzyme
ribonucleotide reductase, which catalyzes the conversion of ribonucleotides to the deoxyribonucleotides required for DNA. Gallium is taken up by the rapidly proliferating cells, but it is not functional for DNA synthesis, so the cells cannot reproduce and they ultimately die by
apoptosis. Normally reproducing cells take up little gallium (as is known from
gallium scans), and gallium is not incorporated into
hemoglobin, accounting for the relatively low toxicity of gallium.[5]
Research
Gallium (III) ion shows anti-inflammatory activity in animal models of inflammatory disease.[2][5][6] Orally administered gallium maltolate has demonstrated efficacy against two types of induced
inflammatory arthritis in rats.[6] Experimental evidence suggests that the anti-inflammatory activity of gallium may be due, at least in part, to down-regulation of pro-inflammatory
T-cells and inhibition of inflammatory cytokine secretion by
macrophages.[2][5][6] Because many iron compounds are pro-inflammatory, the ability of gallium to act as a non-functional iron mimic may contribute to its anti-inflammatory activity.[2]
Gallium maltolate has also been proposed for the treatment for primary liver cancer (
hepatocellular carcinoma; HCC). In vitro experiments demonstrated efficacy against HCC cell lines,[4] and encouraging clinical results have been reported.[7]
Gallium compounds are active against infection-related biofilms, particularly those caused by Pseudomonas aeruginosa.[8][9] In related research, locally administered gallium maltolate has shown efficacy against P. aeruginosa in a mouse burn/infection model.[10] The potential of this approach may be somewhat limited by the relatively rapid appearance of gallium-resistant isolates.[11][12]
Oral gallium maltolate has been investigated as a treatment for Rhodococcus equi foal pneumonia, a common and often fatal disease of newborn horses. R. equi can also infect humans with AIDS or who are otherwise
immunocompromized.[13][14]
Topically applied gallium maltolate has been studied for use in
neuropathic pain (severe
postherpetic neuralgia and
trigeminal neuralgia).[6] It has been hypothesized that any effect on pain may be related to gallium's anti-inflammatory mechanisms, and possibly from its interactions with certain
matrix metalloproteinases and
substance P, whose activities are zinc-mediated and which have been implicated in the etiology of pain.[6]
^
abcdBernstein, L.R. (2005).
"Therapeutic gallium compounds"(PDF). In Gielen, M.; Tiekink, E.R.T. (eds.). Metallotherapeutic Drugs and Metal-Based Diagnostic Agents: The Use of Metals in Medicine. New York: Wiley. pp. 259–277.
ISBN978-0-470-86403-6.