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

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Abstract
In an extension of promising inhibitory results in vitro against H. capsulatum, correlated earlier using substituent constants developed by regression analysis with 77 disulfides, 1 symmetrical and 14 unsymmetrical disulfides were prepared. About half were active in vitro against H. capsulatum (and 1 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 1st 2 also might be used to increase solubility. Earlier inhibitory promise of the morpholino group did not materialize. None was significantly active in vivo. The unsymmetrical disulfides were prepared by reaction of thiols with sulfenyl chlorides or with acyclic or cyclic thiolsulfonates. Two 6-membered heterocyclic disulfides 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.