Clioquinol

Mao et al. identified the off-patented drugs clioquinol [104] and cyproheptadine [105] as potential therapeutics for both myeloma and leukemia. 

Using both traditional medicinal chemistry and parallel synthesis, the irutial side activity is transformed into the main activity and, conversely, the irutial main activity is strongly reduced or abolished. 

This strategy has demonstrated a higher probability of yielding safe, bio-available, original, and patentable analogs than conventional de novo screening techniques such as HTS did. 

Contrary to this, the SOSA approach is based on optimization of side activities that are totally different from the original activity of the molecule. 

SOSA together with parallel pharmacophore-based virtual screening or other informatics-based molecular building tools is a straightforward and fairly 

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Clioquinol—used for eczema, athlete s foot, and other fungal infections... 

CyH7NO 148-24-3) see Actinoquinol Broxyquinoline Clioquinol Diiodohydroxyquinoline Halquinol Nitroxoline oxytetracycline... 

Clioquinol Subacute myelo-optic neuropathy Approx 1930 51... 

Treiber, C., Simons, A., Strauss, M., et al. (2004) Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer s disease. J. Biol. Chem., 279, 51958-51964. 

Docusate sodium is a preparation used for softening ear wax before removal. Hydrocortisone is a corticosteroid, whereas gentamicin, neomycin and clioquinol are antibacterial agents. Otitis externa may be managed by the use of antibacterial preparations used alone or in combination with topical corticosteroids. 

Japan Clioquinol Drug used to treat travelers diarrhea found to cause neuropathy as many as 10 000 affected over two decades... 

The halogenated hydroxyquinolines include iodoquinol and clioquinol. Their mechanism of action is unknown. These agents can produce severe neurotoxicity and clioquinol is believed to have been responsible for the neurotoxic syndrome subacute myelo-optic neuropathy (SMON). 

Adverse reactions are related to the iodine content of the drug the toxicity is often expressed as skin reactions, thyroid enlargement, and interference with thyroid function studies. Headache and diarrhea also occur. Chronic use of clioquinol, a closely related agent, has been linked to a myelitislike illness and to optic atrophy with permanent loss of vision. 

Mechanism of Action Clioquinol is a broad-spectrum antibacterial agent but the mechanism of action is unknown. Hydrocortisone is a corticosteroid that diffuses across cell membranes, forms complexes with specific receptors and further binds to DNA and stimulates transcription of mRNA (messenger RNA) and subsequent protein synthesis of various enzymes thought to be ultimately responsible for the anti-inflammatory effects of corticosteroids applied topically to the skin Therapeutic Effect Alters membrane function and produces antibacterial activity Pharmacokinetics Clioquinol may be absorbed through the skin in sufficient amounts. 

Cream 3% clioquinol and 0.5% hydrocortisone (Ala-Quin, Vioform-Hydrocortisone Mild Cream) 3% clioquinol and 1% hydrocortisone (Vioform-Hydrocortisone Cream, Dek-Quin). 

Ointment 3% clioquinol and 1% hydrocortisone (Vioform-Hydrocortisone Mild Ointment). 

I Contraindications Lesions of the eye, tuberculosis of skin, diaper rash, hypersensitivity to clioquinol or hydrocortisone or any other component of the formulation... 

Bendrofluazide (bendroflumethiazide) Clioquinol (iodochlorhydroxyquin) Sodium cromoglycate (cromolyn sodium) Debrisoquine (debrisoquin)... 

A neuropathy caused by clioquinol (iodochlorohydroxyquin, chinoform) and enhanced by the formation of a clioquinol ferric chelate which initiates lipid peroxidation, leads to complete degeneration of retinal neuroblasts within a day. Vitamin E has a potent protective action against the effects of the chelate [75]. Peroxidative damage to DNA in rat brain, induced by methyl ethyl ketone peroxide, a potent initiator of lipid peroxidation, was inhibited by addition of vitamin E to the diet of rats [76]. 

Chelating agents E.g. desferroxamine, clioquinol Some improvements in cognitive function... 

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