Effects of various compounds on growth of yeast cells of Histoplasma capsulatum

Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and for their ability to inhibit malate dehydrogenase as an intracellular target enzyme model. Correlation analysis indicates that ascites cell inhibition is linearly related to pi and that malate dehydrogenase inhibition is linearly related to MR.

mentioning

confidence: 99%

Design, synthesis, and correlation analysis of 7-substituted 4-hydroxyquinoline-3-carboxylic acids as inhibitors of cellular respiration

Shah¹,

Coats²

1977

“…Since the o-carboxyphenylthio moiety (2) is a promising latentiating group for biologically active thiols, its use to latentiate 1 deserved attention. Table I shows two target compounds selected, 3 and 4, along with other compounds tested as discussed below.…”

mentioning

confidence: 99%

“…An effort to prepare 2-chloroethyl 2-(n-decylamino)ethyl disulfide hydrochloride, containing two promising groups,36 by reaction of 2-chloroethanesulfenyl chloride and 2-(n-de- Evidence that the unsymmetrical disulfides were not 1:1 mixtures of the two symmetrical ones was afforded by good agreement with the reported melting point for the known compounds 7, 9, 10, 12, and 15. For the others, at least three of the following were applicable, depending on the circumstances: (1) use of well-established methods of preparation and purification; (2) proper elemental analysis (possible only for the unsymmetrical disulfide or in the improbability that a precise 1:1 ratio of the symmetrical ones would survive purification); (3) significant differences in solubility of the unsymmetrical disulfide from one or both symmetrical ones; (4) all previously unknown unsymmetrical disulfides showed only one spot in TLC; (5) sharp melting point (not characteristic of a mixture);16 (6) study of disproportionation.…”

mentioning

confidence: 99%

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

Field¹,

Grimaldi²,

Hanley³

et al. 1977

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).

“…mk\i gives ß' » + ^' ^ ! + ... + ™*/ = fe fe fe ^6# (6) k which are solved for µ', x-¿, ... , y /. It is clear that trouble will arise if a pair of substituents X, and Y; each appear only once and are in the same molecule, since the one experimental value of / cannot give two parameters x,7 and y/.…”

mentioning

confidence: 99%

Linear regression analysis of inhibitory potency of organic disulfides against Histoplasma capsulatum

Lj¹,

Rh²,

Dillon³

et al. 1975