Thiol-containing compounds for the removal of elements from tissues and formulations therefor
Methods and pharmaceutical formulations for ameliorating heavy metal toxicity and/or oxidative stress are disclosed, comprising administering pharmaceutically effective amounts of ligands according to the present disclosure. The ligands are of the general structure: where R 1 comprises benzene, pyridine, pyridin-4-one, naphthalene, anthracene, phenanthrene or alkyl groups, R 2 comprises hydrogen, alkyls, aryls, a carboxyl group, carboxylate esters, organic groups or biological groups, R 3 comprises alkyls, aryls, a carboxyl group, carboxylate esters, organic groups or biological groups, X comprises hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, alkyls, aryls, a carboxyl group, carboxylate esters, thiophosphate, N-acetyl cysteine, mercaptoacetic acid, mercaptopropionic acid, thiolsalicylate, organic groups or biological groups, n independently equals 1-10, m=1-6, Y comprises hydrogen, polymers, silicas or silica supported substrates, and Z comprises hydrogen, alkyls, aryls, a carboxyl group, carboxylate esters, a hydroxyl group, NH 2 , HSO 3 , halogens, a carbonyl group, organic groups, biological groups, polymers, silicas or silica supported substrates.
1. A method for ameliorating heavy metal toxicity in a mammal, comprising administering to the mammal a pharmaceutically effective amount of a compound having a chemical formula:
where R 1 is selected from the group consisting of benzene, pyridine, pyridin-4-one, naphthalene, anthracene, and phenanthrene groups, R 2 is independently selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, and carboxylate esters, R 3 is independently selected from the group consisting of benzene alkyls, aryls, a carboxyl group, and carboxylate esters, X is independently selected from the group consisting of benzene hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, alkyls, aryls, a carboxyl group, carboxylate esters, cysteine, homocysteine, glutathione, lipoic acid, dihydrolipoic acid, thiophosphate, N-acetyl cysteine, mercaptoacetic acid, mercaptopropionic acid, γ-glutamyl cysteine, phytochelatins, and thiolsalicylate, n independently equals 1-10, m=2, 4, 5, or 6, Y is independently selected from the group consisting of hydrogen, polymers, silicas and silica supported substrates, and Z is selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, carboxylate esters, a hydroxyl group, NH 2 , HSO 3 , halogens, a carbonyl group, polymers, silicas and silica supported substrates.
2. The method of claim 1 , wherein m=2.
3. The method of claim 2 , wherein at least one R 3 is a carboxyl group.
4. The method of claim 3 , wherein at least one X is glutathione.
5. The method of claim 3 , wherein at least one R 3 is a carboxylic acid, a methyl-ester or an ethyl-ester.
6. The method of claim 1 , wherein both R 2 are hydrogen, both R 3 are a carboxyl group, both X are glutathione and both n equal 1.
7. The method of claim 1 , wherein R 1 is benzene.
8. The method of claim 1 , including selecting a route of administration from at least one of the group consisting of oral, transmucosal, transdermal, nasal, suppository, intravenous, and combinations thereof.
9. The method of claim 8 , including administering between about 0.5 and 100 milligrams of the compound per kilogram of the mammal's total body weight.
10. The method of claim 9 , including administering between about 0.5 and 60 milligrams of the compound per kilogram of the mammal's total body weight.
11. A method for relieving oxidative stress in a mammal, comprising administering to the mammal a pharmaceutically effective amount of a compound having a chemical formula:
where R 1 is selected from the group consisting of benzene, pyridine, pyridin-4-one, naphthalene, anthracene, and phenanthrene groups, R 2 is independently selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, and carboxylate esters, R 3 is independently selected from the group consisting of benzene alkyls, aryls, a carboxyl group, and carboxylate esters, X is independently selected from the group consisting of benzene hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, alkyls, aryls, a carboxyl group, carboxylate esters, cysteine, homocysteine, glutathione, lipoic acid, dihydrolipoic acid, thiophosphate, N-acetyl cysteine, mercaptoacetic acid, mercaptopropionic acid, γ-glutamyl cysteine, phytochelatins, and thiolsalicylate, n independently equals 1-10, m=2, 4, 5, or 6, Y is independently selected from the group consisting of hydrogen, polymers, silicas and silica supported substrates, and Z is selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, carboxylate esters, a hydroxyl group, NH 2 , HSO 3 , halogens, a carbonyl group, polymers, silicas and silica supported substrates.
12. The method of claim 11 , wherein m=2.
13. The method of claim 12 , wherein at least one R 3 is a carboxyl group.
14. The method of claim 13 , wherein at least one X is glutathione.
15. The method of claim 13 , wherein at least one R 3 is a carboxylic acid, a methyl-ester or an ethyl-ester.
16. The method of claim 11 , wherein R 1 is benzene.
17. The method of claim 11 , including selecting a route of administration from at least one of the group consisting of oral, transmucosal, transdermal, nasal, suppository, intravenous, and combinations thereof.
18. The method of claim 17 , including administering between about 0.5 and 100 milligrams of the compound per kilogram of the mammal's total body weight.
19. The method of claim 18 , including administering between about 0.5 and 60 milligrams of the compound per kilogram of the mammal's total body weight.
20. The method of claim 14 , wherein at least one R 3 is a carboxyl group.
21. A method for ameliorating heavy metal toxicity in a mammal, comprising administering to the mammal a pharmaceutically effective amount of a compound having a chemical formula:
where R 1 is selected from the group consisting of benzene, pyridine, pyridin-4-one, naphthalene, anthracene, and phenanthrene groups, R 2 is independently selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, and carboxylate esters, R 3 is independently selected from the group consisting of benzene alkyls, aryls, a carboxyl group, and carboxylate esters, X is independently selected from the group consisting of benzene hydrogen, lithium, sodium, potassium, rubidium, cesium, francium, alkyls, aryls, a carboxyl group, carboxylate esters, cysteine, homocysteine, glutathione, lipoic acid, dihydrolipoic acid, thiophosphate, N-acetyl cysteine, mercaptoacetic acid, mercaptopropionic acid, γ-glutamyl cysteine, phytochelatins, and thiolsalicylate, n independently equals 1-10, m=2, 4, 5, or 6, Y is independently selected from the group consisting of hydrogen, polymers, silicas and silica supported substrates, and Z is selected from the group consisting of hydrogen, alkyls, aryls, a carboxyl group, carboxylate esters, a hydroxyl group, NH 2 , HSO 3 , halogens, a carbonyl group, polymers, silicas and silica supported substrates;
wherein at least one of said R 3 and said X group is selected whereby a property of hydrophobicity or hydrophilicity of said compound is selectively altered, said property of hydrophobicity or hydrophilicity in turn determining whether said compound having a heavy metal bound thereto is cleared from the mammal body via a fecal route or a kidney route.
22. The method of claim 21 , wherein m=2.
23. The method of claim 22 , wherein at least one R 3 is a methyl-ester or an ethyl-ester.
24. The method of claim 21 , wherein R 1 is benzene.
25. The method of claim 21 , including selecting a route of administration from at least one of the group consisting of oral, transmucosal, transdermal, nasal, suppository, intravenous, and combinations thereof.