8-Hydroxy-7-iodo-5-quinolinesulfonic acid

New insights into the mechanism of antifungal action of 8-hydroxyquinolines.[Pubmed:30662305]

Saudi Pharm J. 2019 Jan;27(1):41-48.

The 8-hydroxyquinoline core is a privileged scaffold for drug design explored to afford novel derivatives endowed with biological activity. Our research aimed at clarifying the antifungal mechanism of action of clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-Hydroxy-7-iodo-5-quinolinesulfonic acid (three 8-hydroxyquinoline derivatives). The antifungal mode of action of these derivatives on Candida spp. and dermatophytes was investigated using sorbitol protection assay, cellular leakage effect, ergosterol binding assay, and scanning electron microscopy. Clioquinol damaged the cell wall and inhibited the formation of pseudohyphae by C. albicans. The 8-hydroxy-5-quinolinesulfonic acid derivatives compromised the functional integrity of cytoplasmic membranes. To date no similar report was found about the antifungal mechanism of 8-hydroxyquinolines. These results, combined with the broad antifungal spectrum already demonstrated previously, reinforce the potential of 8-hydroxyquinolines for the development of new drugs.

Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design.[Pubmed:28159993]

Med Mycol. 2017 Oct 1;55(7):763-773.

Clioquinol is an 8-hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti-Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8-hydroxyquinoline derivatives (8-hydroxy-5-quinolinesulfonic acid and 8-Hydroxy-7-iodo-5-quinolinesulfonic acid). Antifungal activity was tested by broth microdilution and the fungicidal or fungistatic effect was checked by a time-kill assay. Permeation and histopathological evaluation were performed in Franz diffusion cells with ear skin of pigs and examined under light microscopy. An HET-CAM test was used to determine the potential irritancy. The three compounds were active against all isolates showing anti-Candida and antidermatophyte activity, with MIC ranges of 0.031-2 mug/ml, 1-512 mug/ml, and 2-1024 mug/ml for clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-Hydroxy-7-iodo-5-quinolinesulfonic acid, respectively. All compounds showed fungistatic effect for Candida, 8-hydroxy-5-quinolinesulfonic acid, and 8-Hydroxy-7-iodo-5-quinolinesulfonic acid showed a fungicidal effect for M. canis and T. mentagrophytes, and clioquinol showed a fungicidal effect only for T. mentagrophytes. Furthermore, they presented a fungicidal effect depending on the time and concentration. The absence of lesions was observed in histopathological evaluation and no compound was irritating. Moreover, clioquinol and 8-hydroxy-5-quinolinesulfonic acid accumulated in the epithelial tissue, and 8-Hydroxy-7-iodo-5-quinolinesulfonic acid had a high degree of permeation. In conclusion, 8-hydroxyquinoline derivatives showed antifungal activity and 8-hydroxy-5-quinolinesulfonic acid demonstrated the potential for antifungal drug design.

Aluminum polymers formed following alum treatment of lake water.[Pubmed:20825969]

Chemosphere. 2010 Nov;81(7):832-6.

Alum (aluminum sulfate) is increasingly being used in lake management to control internal recycling of phosphorus from bottom sediments. Alum added to water undergoes rapid hydrolysis reactions, forming an amorphous Al(OH)3 floc with a high capacity for sorption of phosphorus. While it is known that the Al(OH)3 floc transforms over time to more ordered microcrystalline and crystalline gibbsite phases, there remains an incomplete understanding of the forms of Al present immediately following alum addition to lake water. A laboratory study was thus undertaken to evaluate the forms of Al present following alum addition using ferron (8-Hydroxy-7-iodo-5-quinolinesulfonic acid) timed-colorimetric and 27Al-NMR measurements. A polymeric Al species with moderate reactivity with ferron (Alb2) was initially formed, although it rapidly transformed to a less ferron-reactive colloidal form (Alc) and also decomposed at low alum doses to monomeric Al (Ala) in response to pH increases associated with outgassing of CO2. The Ala fraction in these solutions could be adequately estimated based upon measured pH assuming Al solubility was controlled by an amorphous Al(OH)3 phase. Al13 was inferred from ferron measurements to be present, but only at quite low concentrations in the alum-treated waters.

Six spectroscopic methods for detection of oxidants in urine: implication in differentiation of normal and adulterated urine.[Pubmed:15516320]

J Anal Toxicol. 2004 Oct;28(7):599-608.

Six separate methods to detect oxidants in urine were developed. The presence of the oxidants was established by initial oxidation of ferrous to ferric ion and detecting the ferric by chromogenic oxidation or complex formation. The reagents for chromogenic oxidation were N,N-dimethylamoino-1,4-phenylenediamine (DMPDA), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS), and 2-amino-p-cresol (APC), and the reagents for the chromogenic complex were xylenol orange (XO), 8-Hydroxy-7-iodo-5-quinolinesulfonic acid (HIQSA), and 4,5-dihydroxy-1,3-benzene-di-sulfonic acid (HBSA). All methods showed comparable results when tested for ferric, chromate, permanganate, oxychloride, hydrogen peroxide, oxone, tert-butylhydroperoxide, and cumenehydroperoxide at a concentration of 1.0 mmol/L in water (CV < 7%). The nitrite results are comparable only with DMPDA and APC. Periodate responded to the highest oxidation number (ON = 8) by chromogenic oxidation but lowest (ON = 2) by the chromogenic complex. The iodate responded only to the chromogenic oxidation with ON = 6. The linearity of the procedures was established by chromate in water. The linear concentrations were 0.09-12.00 mE/L for DMPDA, ABTS, APC, and HBSA and 0.09-6.00 mE/L for XO and HIQSA. In all methods, the correlation coefficients were > or = 0.9991 and precisions were within +/- 5.6%. The methods were used to test oxidants in 238 urine specimens. The chromate at 3.0 mE/L in water was used as standard. The correlation coefficients of 0.9600-0.9853 and the ANOVA test (F = 0.90, F(critical) = 2.22 at P(0.48)) indicated that the methods correlated well. The median concentration of oxidants in the specimens was 0.21 mE/L with an average and standard deviation of 0.62 +/- 1.19 (range 0.04-8.83 mE/L). When Grubbs' statistical test was applied to the specimen results, no specimen was found to be outlier or could be considered as adulterated. The Grubbs' test also revealed that the threshold concentration to identify urine adulteration was 29 mE/L at confidence level of 99%.

Assessing the Rhizotoxicity of the Aluminate Ion, Al(OH)(4).[Pubmed:16667665]

Plant Physiol. 1990 Aug;93(4):1620-5.

Dissolved aluminum (III) in acidic soils or culture media is often rhizotoxic (inhibitory to root elongation). Alkaline solutions of Al are also sometimes rhizotoxic, and for that reason toxicity has been attributed to the aluminate ion, Al(OH)(4) (-). In the present study, seedlings of wheat (Triticum aestivum L. cv Tyler) and red clover (Trifolium pratense L. cv Kenland) were cultured in aerated aluminate solutions at pH 8.0 to 8.9. The bulk phases of these solutions were free of reactive polynuclear hydroxy-Al (including the extremely toxic species AlO(4)Al(12)[OH](24)[H(2)O](7+) (12) [Al(13)]) according to the ferron (8-Hydroxy-7-iodo-5-quinolinesulfonic acid) assay. At an aluminate concentration of 25 micromolar (23 micromolar activity) and a pH of 8, root elongation was less than 40% of Al-free controls, but at pH 8.9 elongation was 100% of controls. The hypothesis is offered that aluminate is nontoxic and that the inhibition at lower pH values is attributable to Al(13) postulated to have formed in the acidic free space of the roots where the ratio /{Al(3+)/}//{H(+)/}(3) may rise above 10(10). At this value hydroxy-Al in over-saturated, alkaline solutions begins to undergo rapid conversion to polynuclear species.