Pairing pain medicine with metal ions to battle cancer

February 17, 2016
Pairing pain medicine with metal ions to battle cancer

Fighting chemoresistant cancer remains a huge challenge that scientists are tackling from as many angles as they can. One alternative approach involves pairing two groups of compounds—pain medicine and metal ions—that have individually shown promise as anti-cancer agents. Scientists report in the ACS journal Inorganic Chemistry that combining the two led to new compounds that could destroy drug-resistant cancer cells and leave most normal cells alone in lab tests.

Using metal ions in cancer drugs has a relatively long history. Cisplatin, for example, is a platinum-based therapy that has been used for years against lung, ovary and other cancers. But often, resistance against the drug develops. Recent advances, however, are pointing to new ways to destroy . Metal complexes other than platinum-based ones have emerged as potential cancer fighters. And studies have found that (NSAIDs) work against certain cancers and boost the activity of other drugs. Paul J. Dyson and colleagues decided to link the NSAIDs indomethacin and diclofenac with ruthenium and osmium ions to see if they could come up with an effective combination.

The researchers created several different NSAID-metal ion complexes, characterized their structures and tested them in the lab for their cancer-fighting potential. Some compounds were even more effective against than cisplatin. And a few were significantly more toxic to cisplatin-resistant cells than to healthy cells, an important factor that could potentially reduce side effects down the road.

Explore further: Precious metal could lead to next generation of cancer treatments

More information: Emilia Păunescu et al. Nonsteroidal Anti-inflammatory—Organometallic Anticancer Compounds, Inorganic Chemistry (2016). DOI: 10.1021/acs.inorgchem.5b02690

Abstract
Compounds that combine metal-based drugs with covalently linked targeted organic agents have been shown, in some instances, to exhibit superior anticancer properties compared to the individual counterparts. Within this framework, we prepared a series of organometallic ruthenium(II)- and osmium(II)-p-cymene complexes modified with the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin and diclofenac. The NSAIDs are attached to the organometallic moieties via monodentate (pyridine/phosphine) or bidentate (bipyridine) ligands, affording piano-stool Ru(II) and Os(II) arene complexes of general formula [M(η6-p-cymene)Cl2(N)], where N is a pyridine-based ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-3-(pyridin-3-yl)propanoate}, [M(η6-p-cymene)Cl2(P)], where P is a phosphine ligand, {2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate} or {2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl-4-(diphenylphosphanyl)benzoate, and [M(η6-p-cymene)Cl(N,N′)][Cl], where N,N′ is a bipyridine-based ligand, (4′-methyl-[2,2′-bipyridin]-4-yl)methyl-2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate), (4′-methyl-[2,2′-bipyridin]-4-yl)methyl-2-(2-((2,6-dichlorophenyl)amino)phenyl)acetate), (bis(2-(2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetoxy)ethyl)[2,2′-bipyridine]-5,5′-dicarboxylate), or (bis(2-(2-(2-((2,6-dichlorophenyl)amino)phenyl)acetoxy)ethyl)[2,2′-bipyridine]-5,5′-dicarboxylate). The antiproliferative properties of the complexes were assessed in human ovarian cancer cells (A2780 and A2780cisR, the latter being resistant to cisplatin) and nontumorigenic human embryonic kidney (HEK-293) cells. Some of the complexes are considerably more cytotoxic than the original drugs and also display significant cancer cell selectivity.

Related Stories

Metals could forge new cancer drug

October 19, 2009

Drugs made using unusual metals could form an effective treatment against colon and ovarian cancer, including cancerous cells that have developed immunity to other drugs, according to research at the University of Warwick ...

Recommended for you

Spiders spin unique phononic material

July 25, 2016

New discoveries about spider silk could inspire novel materials to manipulate sound and heat in the same way semiconducting circuits manipulate electrons, according to scientists at Rice University, in Europe and in Singapore.

A tiny answer to the counterfeit drug problem

July 25, 2016

The counterfeit drug industry is thriving. Criminals are cashing in on an estimated $200 billion in profits – nearly 10 percent of pharmaceuticals worldwide – while unknowing consumers put their health or even lives at ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.