Organic disulfides and related substances. XXXVIII. Some disulfide and trisulfide sulfinate salts as antiradiation drugs. [Gamma radiation]

Journal Article · Fri Aug 01 04:00:00 EDT 1975 · J. Med. Chem.; (United States)

DOI:https://doi.org/10.1021/jm00242a008· OSTI ID:7354745

Srivastava, P K ^[1]; Field, L; Grenan, M M

---

1. Vanderbilt Univ., Nashville

The trisulfide disulfinate (NaO/sub 2/S(CH/sub 2/)/sub 4/S)/sub 2/S (2) is an antiradiation drug which is atypical in having no nitrogen function. At low dose levels of 37.5 and 18.8 mg/kg intraperitoneally (ip), 2 protected respectively about 82 and 35 percent of lethally irradiated mice. By the oral route (po), 150 mg/kg of 2 protected about 73 percent, and 75 mg/kg protected about 20 percent. The LD/sub 50/ either ip or po exceeded 900 mg/kg. Although a 2,3-diacetoxy analog 3 was inactive, cyclic disulfide and trisulfide sulfinate analogs showed promise. Among these, a sulfinate moiety is related to a di- or trisulfide moiety in the sense of 1,8 in a naphthyl system (4,5), 2,2' in a biphenyl system (6-9), and ..cap alpha..,..cap alpha..' in an o-xylyl system (10,11). The 1,8-naphthyl disulfide sulfinate 4 was not tested biologically because a marked neighboring group effect of -SO/sub 2/Na on --SS- caused rapid cyclization to the parent disulfide dioxide 14; the corresponding trisulfide 5 was more stable but only slightly protective. Other compounds that lack the usual nitrogen function show antiradiation properties. The fact that sulfinate salts show activity, both ip and po, suggests that the -SO/sub 2/Na moiety deserves more attention in medicinal chemistry. Hydration of sulfinate salts often made analytical characterization difficult. Confirmatory evidence for typical structures is given. and po routes (e.g., given ip, 10 led to 93-100 percent survival at 75 mg/kg, with LD/sub 50/ greater than 950 mg/kg; given po, 10 gave 100 percent survival at 600 mg/kg, with LD/sub 50/ greater than 900 mg/kg). Compounds 7 and 11 join 2 as promising antiradiation drugs that lack the usual nitrogen function. The fact that sulfinate salts show activity, both ip and po, suggests that the -SO/sub 2/Na moiety deserves more attention in medicinal chemistry. Hydration of sulfinate salts often made analytical characterization difficult. Confirmatory evidence for typical structures is given.

• OSTI ID: 7354745
• Journal Information: J. Med. Chem.; (United States), Journal Name: J. Med. Chem.; (United States) Vol. 18:8; ISSN JMCMA
• Country of Publication: United States
• Language: English

Related Subjects

560152* -- Radiation Effects on Animals-- Animals
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
CHALCOGENIDES
CHEMICAL PROPERTIES
CHEMICAL REACTIONS
CRYOGENIC FLUIDS
DISULFIDES
DOSES
DRUGS
ELECTROMAGNETIC RADIATION
ELEMENTS
FLUIDS
GAMMA RADIATION
IONIZING RADIATIONS
LETHAL DOSES
LETHAL RADIATION DOSE
MAMMALS
MICE
NITROGEN
NONMETALS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
RADIATION DOSES
RADIATION EFFECTS
RADIATION PROTECTION
RADIATIONS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS
RODENTS
SULFIDES
SULFUR COMPOUNDS
SURVIVAL TIME
VERTEBRATES