Curcumin analogue identified as hyaluronan export inhibitor by virtual docking to the ABC transporter MRP5.

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Prehm P

Curcumin analogue identified as hyaluronan export inhibitor by virtual docking to the ABC transporter MRP5.

Food Chem Toxicol. 2013 Dec;62:76-81. doi: 10.1016/j.fct.2013.08.028. Epub 2013 Aug 24.

PubMed ID

23978416 [ View in PubMed

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Abstract

Hyaluronan is overproduced in many diseases including metastasis, inflammation or ischemia, but there is no drug to attenuate hyaluronan production. Hyaluronan is exported from fibroblasts by the multidrug resistance associated protein 5 (MRP5) which is inhibited by the plant phenols curcumin or xanthohumol. We performed virtual docking and chemical synthesis of analogues to optimize the inhibitors. The AutoDock software was used to identify the binding cavity within the open conformation of MRP5. Inhibitory plant phenols bound to the ATP binding site between the two nucleotide binding domains NBD1 and NBD2. This binding cavity was chosen to screen about 120 derivatives and analogues. The superior hyaluronan export inhibitor was 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (hylin). It inhibited hyaluronan export from fibroblasts with an IC50 of 4.9 muM. Hylin is a minor component in natural curcumin preparations and has previously been described as anti-metastatic and anti-inflammatory. Since curcumin itself is unstable under physiological conditions, the active component for many cell biological and pharmaceutical effects of natural curcumin preparations could be hylin that acts by hyaluronan export inhibition.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Curcumin	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Inhibitor	Details
Curcumin sulfate	Multidrug resistance-associated protein 5	Protein	Humans	Unknown	Not Available	Details