Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

Journal Article · Tue Sep 01 00:00:00 EDT 1992 · The Annals of Pharmacotherapy; (United States)

OSTI ID:6703977

Foye, W O ^[1]

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1. Massachusetts College of Pharmacy and Allied Health Sciences, Boston (United States)

Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS was determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.

• OSTI ID: 6703977
• Journal Information: The Annals of Pharmacotherapy; (United States), Vol. 26:9
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GAMMA RADIATION
LETHAL DOSES
RADIOPROTECTIVE SUBSTANCES
SYNTHESIS
AMPHETAMINES
ANIMALS
CALCULI
CHEMOTHERAPY
COPPER
DRUGS
ELECTROPHORESIS
HUMAN POPULATIONS
INHIBITION
KIDNEYS
MICE
MUCOPOLYSACCHARIDES
NITROGEN
PATIENTS
PHARMACOLOGY
SULFATION
SULFUR
SULFUR COMPOUNDS
SUPEROXIDE DISMUTASE
WHOLE-BODY IRRADIATION
AMINES
ANALEPTICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOHYDRATES
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL REACTIONS
DOSES
ELECTROMAGNETIC RADIATION
ELEMENTS
ENZYMES
EXTERNAL IRRADIATION
IONIZING RADIATIONS
IRRADIATION
MAMMALS
METALS
NONMETALS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
POLYSACCHARIDES
POPULATIONS
PROTEINS
RADIATIONS
RODENTS
SACCHARIDES
SYMPATHOMIMETICS
THERAPY
TRANSITION ELEMENTS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture