Biologically oriented organic sulfur chemistry. 9. Carbonyl and thiocarbamoyl disulfides as inhibitory agents for Histoplasma capsulatum

Abstract

Dithiocarbamates and thiuram disulfides have long been noted for antifungal activity against human pathogens.1 2 More specifically, potassium N,N-dimethyldithiocarbamate inhibited Histoplasma capsulaban at <10 Mg/ml in vitro, and some trithiopercarbamates, IVIDNCfSlSSR3, at 1-5 ag/ml.3 Thioacetic and thiopropionic acid also inhibited H. capsulatum (10-20 yug/ml).4 5Latentiation of thioacetic and other thio acids as the carbonyl disulfides, R^CfO)-SSR2, produced compds having in vitro activity at conens ranging upward from 8 ag/ml, suggesting that R2S moieties without functional groups were not particularly promising for latentiation.6 Since the moiety S(CH2)r S02Na gave quite good results when used to latentiate a radioprotective thiol, 2-acetamidoethanethiol,6 this moiety seemed a worthwhile one to try with dithiocarbamates and a thio acid.Compds 2-5 (Table I) were prepared by oxodisulfide cleavage,6 in which the appropriate thiolate reacts with 1,2-dithiane 1,1-dioxide (1), as shown by eq 1; these reactions thus extend oxodisulfide cleavage to include thio and dithiocarbamic acid salts. RC(X)SNa + (CH,)4S0,S RC(X)SS(CH2)4SO,Na

Organic disulfides and related substances. 45. Synthesis and properties of some disulfide sulfinate salts containing no nitrogen

“…General. Procedures for the preparation of the disulfide sulfinate salts 2-11 can be exemplified by the preparation below of sodium 4-(n -decyldithio)butanesulfinate (2). Significant variations from this procedure are reported under individual disulfide sulfinate salts.…”

“…Several disulfide sulfinate salts of the general structure RSS(CH2)4S02Na afford promising mammalian protection against ionizing radiation (1)(2)(3)(4)(5)(6). This paper reports new types of disulfide sulfinates obtained by reaction of 1,2-dithiane 1,1dioxide (1) with heretofore unexplored types of thiols, in a search for radioprotective agents that lack the nitrogen functions believed to cause adverse effects (Scheme I); once optimum thiols are known, the model dioxide 1 can be replaced by other dioxides.…”

Forty-Five Years With a Hydra, Organosulfur Chemistry

“…5). 24 Sulfenyl halides sometimes gave better results, however (eq. 6);" for example, the approach of - eq.…”

“…'~*~~~~~~~ N evertheless, disproportionation can occur,42 and some unsymmetrical disulfides are unstable as solids, even in the dark under N2. 24 Tables 1-3 show that these disulfides ordinarily disproportionate much more rapidly in water than in alcohols and in alcohols more rapidly than in inert solvents; with salts such as those containing -S02Na, this effect may reflect increased ion pairing in nonaqueous solvents (and thus less neigh-…”