Gallium maltolate is a

coordination complex A coordination complex is a chemical compound consisting of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of chemical bond, bound molecules or ions, that are in turn known as ' ...

consisting of a trivalent

gallium Gallium is a chemical element; it has Chemical symbol, symbol Ga and atomic number 31. Discovered by the French chemist Paul-Émile Lecoq de Boisbaudran in 1875, elemental gallium is a soft, silvery metal at standard temperature and pressure. ...

cation coordinated to three

maltol Maltol is a naturally occurring organic compound that is used primarily as a flavor enhancer. It is found in nature in the bark of larch trees and in the needles of pine trees, and is produced during the roasting of malt (from which it gets its n ...

ate

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

s. The compound is a potential therapeutic agent for cancer, infectious disease, and inflammatory disease. 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 The ''n''-octanol-water partition coefficient, ''K''ow is a partition coefficient for the two-phase system consisting of ''n''-octanol and water. ''K''ow is also frequently referred to by the symbol P, especially in the English literature. It is a ...

= 0.41).

Mechanism of action

Gallium maltolate delivers gallium with higher oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

than that of gallium salts such as gallium nitrate and

gallium trichloride Gallium(III) chloride is an inorganic chemical compound with the formula which forms a monohydrate, . Solid gallium(III) chloride is a deliquescent colorless crystals and exists as a dimer with the formula . It is colourless and soluble in virtu ...

. ''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 Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

synthesis, as it is present in the active site of the enzyme

ribonucleotide reductase Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase, is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of the ribos ...

, 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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. Normally reproducing cells take up little gallium (as is known from

gallium scan A gallium scan is a type of nuclear medicine diagnostic investigation that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. The gamma emission o ...

s), and gallium is not incorporated into

hemoglobin Hemoglobin (haemoglobin, Hb or Hgb) is a protein containing iron that facilitates the transportation of oxygen in red blood cells. Almost all vertebrates contain hemoglobin, with the sole exception of the fish family Channichthyidae. Hemoglobin ...

, accounting for the relatively low toxicity of gallium.

Research

Gallium (III) ion shows anti-inflammatory activity in animal models of inflammatory disease. Orally administered gallium maltolate has demonstrated efficacy against two types of induced

inflammatory arthritis Inflammatory arthritis is a group of diseases which includes: rheumatoid arthritis, psoriatic arthropathy, inflammatory bowel disease, adult-onset Still's disease, scleroderma, juvenile idiopathic arthritis, and systemic lupus erythematosus (SLE). ...

in rats. Experimental evidence suggests that the anti-inflammatory activity of gallium may be due, at least in part, to down-regulation of pro-inflammatory

T-cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their ce ...

s and inhibition of inflammatory cytokine secretion by

macrophages Macrophages (; abbreviated MPhi, φ, MΦ or MP) are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris and foreign substances, which do not have proteins that ...

. 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. Gallium maltolate has also been proposed for the treatment for primary liver cancer (

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. HCC most common ...

; HCC). ''In vitro'' experiments demonstrated efficacy against HCC cell lines, and encouraging clinical results have been reported. Gallium compounds are active against infection-related biofilms, particularly those caused by ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

''. In related research, locally administered gallium maltolate has shown efficacy against ''P. aeruginosa'' in a mouse burn/infection model. The potential of this approach may be somewhat limited by the relatively rapid appearance of gallium-resistant isolates. 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. Topically applied gallium maltolate has been studied for use in

neuropathic pain Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuo ...

(severe

postherpetic neuralgia Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus ( herpes zoster, also known as shingles). PHN is defined as pain in a dermatomal distributi ...

and

trigeminal neuralgia Trigeminal neuralgia (TN or TGN), also called Fothergill disease, tic douloureux, trifacial neuralgia, is a chronic pain, long-term pain disorder that affects the trigeminal nerve, the nerve responsible for sensation in the face and motor funct ...

). 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 metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...

s and

substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a type of neuropeptide, belonging to the tachykinin family of neuropeptides. It acts as a neurotransmitter and a neuromodulator. Substance P ...

, whose activities are zinc-mediated and which have been implicated in the etiology of pain.

References

{{reflist

External links

Gallixa official site
Gallium compounds Coordination complexes 4-Pyrones