Biologically oriented organic sulfur chemistry. 15. Organic disulfides and related substances. 41. Inhibition of the fungal pathogen Histoplasma capsulatum by some organic disulfides

Abstract

In an extension of promising inhibitory results in vitro against Histoplasma capsulatum, correlated earlier using substituent constants developed by regression analysis with 77 disulfides, one symmetrical and 14 unsymmetrical disulfides were prepared (3--17). About half were active in vitro against H. capsulatum (and one against Candida albicans). Groups that seemed most to lead to promising inhibition among the unsymmetrical disulfides were o-HO2CC6H4, (CH2)4SO2Na, Me2NC(S), p-ClC6H4, and perhaps p-CH3C6H4; the first two also might be used to increase solubility. Earlier inhibitory promise of the morpholino group did not materialize. None of the group 3--17 was significantly active in vivo. The unsymmetrical disulfides were prepared by reaction of thiols with sulfenyl chlorides or with acyclic or cyclic thiosulfonates. Two six-membered heterocyclic disulfides (5 and 6) were prepared by a novel cyclization, in which carbon disulfide reacted with an (N-alkylamino)ethyl Bunte salt, followed by ring closure; an explanation is suggested for formation of a thiazoline when the N-alkyl group is absent. One of the disulfides disproportionated with astonishing ease (31; 0.3--1 h at 25 degrees C).

Benign One‐Pot Synthesis of Carbamo(dithioperoxo)thioate Compounds in Water Medium Using N‐(Arylthio)phthalimides as the Electrophilic Sulfur Source

“…Carbamo(dithioperoxo)thioates, a special class of dithocarbamate compounds with mixed disulfide linkage, have gained extensive importance due to their potential application in the area of medicinal chemistry and drug developments. They were tested to exhibit inhibitory effect on fungal pathogen Histoplasmacapsulatum, and on aldehyde dehydrogenases (ALDH) of sheep liver and human mitochondria . They have also been found to inhibit the expressing of BCA2 in human breast cancer cell line .…”

“…Recently, carbamo(dithioperoxo)thioate derivatives are reported to show anti‐filarial activities. Several methods were attempted to synthesize this special class of compounds but most of the earlier methods,, were not generalized and suffer from unwanted side reactions, complex reaction mixture, long reaction time and low yield of the desired products. There are only two reports of generalized approaches for the synthesis of carbamo(dithioperoxo)thioates using DCM as the reaction medium.…”

Solubility, ionization, and partitioning behavior of unsymmetrical disulfide compounds: Alkyl 2‐imidazolyl disulfides

“…However, group contribution approaches require that the contribution of all structural fragments to the physico‐chemical property of interest be known. Despite the occurrence of the unsymmetrical disulfide fragment in other important experimental groups of drugs,5–8 its contribution to lipophilicity and ionization is still undefined.…”