Synthesis of amphiphilic seleninic acid derivatives with considerable activity against cellular membranes and certain pathogenic microbes

Du, Peng; Viswanathan, Uma M.; Xu, Zhanjie; Ebrahimnejad, Hadi; Hanf, Benjamin; Burkholz, Torsten; Schneider, Marc; Bernhardt, Ingolf; Kirsch, Gilbert; Jacob, Claus

doi:10.1016/j.jhazmat.2014.01.014

Cited by 19 publications

(14 citation statements)

References 38 publications

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“…Indeed, such a concept may be useful to cover: (a) newly identified natural selenium metabolites, such as selenoneine, a rather unusual natural selenium compound which has been found in the blood of tuna and seems to be highly reactive, (b) inorganic selenium species with biological relevance, such as naturally generated selenium nanoparticles found in many strains of Staphylococcus and other bacteria and used on occasion to fortify drinks with selenium, (c) selenium agents currently in development with potential pharmaceutical applications, such as organic seleninic acids, organic selenourea derivatives, selenazolinium salts, and (d) recently discovered selenoproteins and the various modifications of selenocysteine found already or to be expected in those proteins (such as selenosulfide, diselenide, seleninic acids, selenoxides, etc.) [126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142]. Whilst those RSeS at first sight may be less relevant to redox biology compared to RSS because of their number, variety and concentration in most cells and organisms, they are clearly on the rise in the field of food supplementation and pharmaceutical research.…”

Section: Discussionmentioning

confidence: 99%

The Reactive Sulfur Species Concept: 15 Years On

et al. 2017

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Fifteen years ago, in 2001, the concept of “Reactive Sulfur Species” or RSS was advocated as a working hypothesis. Since then various organic as well as inorganic RSS have attracted considerable interest and stimulated many new and often unexpected avenues in research and product development. During this time, it has become apparent that molecules with sulfur-containing functional groups are not just the passive “victims” of oxidative stress or simple conveyors of signals in cells, but can also be stressors in their own right, with pivotal roles in cellular function and homeostasis. Many “exotic” sulfur-based compounds, often of natural origin, have entered the fray in the context of nutrition, ageing, chemoprevention and therapy. In parallel, the field of inorganic RSS has come to the forefront of research, with short-lived yet metabolically important intermediates, such as various sulfur-nitrogen species and polysulfides (Sx2−), playing important roles. Between 2003 and 2005 several breath-taking discoveries emerged characterising unusual sulfur redox states in biology, and since then the truly unique role of sulfur-dependent redox systems has become apparent. Following these discoveries, over the last decade a “hunt” and, more recently, mining for such modifications has begun—and still continues—often in conjunction with new, innovative and complex labelling and analytical methods to capture the (entire) sulfur “redoxome”. A key distinction for RSS is that, unlike oxygen or nitrogen, sulfur not only forms a plethora of specific reactive species, but sulfur also targets itself, as sulfur containing molecules, i.e., peptides, proteins and enzymes, preferentially react with RSS. Not surprisingly, today this sulfur-centred redox signalling and control inside the living cell is a burning issue, which has moved on from the predominantly thiol/disulfide biochemistry of the past to a complex labyrinth of interacting signalling and control pathways which involve various sulfur oxidation states, sulfur species and reactions. RSS are omnipresent and, in some instances, are even considered as the true bearers of redox control, perhaps being more important than the Reactive Oxygen Species (ROS) or Reactive Nitrogen Species (RNS) which for decades have dominated the redox field. In other(s) words, in 2017, sulfur redox is “on the rise”, and the idea of RSS resonates throughout the Life Sciences. Still, the RSS story isn’t over yet. Many RSS are at the heart of “mistaken identities” which urgently require clarification and may even provide the foundations for further scientific revolutions in the years to come. In light of these developments, it is therefore the perfect time to revisit the original hypotheses, to select highlights in the field and to question and eventually update our concept of “Reactive Sulfur Species”.

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Section: Discussionmentioning

confidence: 99%

The Reactive Sulfur Species Concept: 15 Years On

et al. 2017

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“…Importantly, the amphiphilic character of the organic compounds reflects their ability to interact and penetrate biological membranes inducing different effects,29, 32, 46 such as increased antimicrobial activity 47 . Lipophilicity is an important characteristic of antifungal agents, such as terbinafine and ketoconazole, and is also evident in drugs like amphotericin B, which have proven effectiveness to treat systemic fungal infections 46 .…”

Section: Discussionmentioning

confidence: 99%

In vitro antifungal activity of organic compounds derived from amino alcohols against onychomycosis

Caneschi

Almeida

Martins

et al. 2017

Brazilian Journal of Microbiology

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Onychomycosis is a fungal infection of the nail caused by high densities of filamentous fungi and yeasts. Treatment for this illness is long-term, and recurrences are frequently detected. This study evaluated in vitro antifungal activities of 12 organic compounds derived from amino alcohols against standard fungal strains, such as Trichophyton rubrum CCT 5507 URM 1666, Trichophyton mentagrophytes ATCC 11481, and Candida albicans ATCC 10231. The antifungal compounds were synthesized from p-hydroxybenzaldehyde (4a–4f) and p-hydroxybenzoic acid (9a–9f). Minimum inhibitory concentrations and minimum fungicidal concentrations were determined according to Clinical and Laboratory Standards Institute protocols M38-A2, M27-A3, and M27-S4. The amine series 4b–4e, mainly 4c and 4e compounds, were effective against filamentous fungi and yeast (MIC from 7.8 to 312 μg/mL). On the other hand, the amide series (9a–9f) did not present inhibitory effect against fungi, except amide 9c, which demonstrated activity only against C. albicans. This allowed us to infer that the presence of amine group and intermediate carbon number (8C–11C) in its aliphatic side chain seems to be important for antifungal activity. Although these compounds present cytotoxic activity on macrophages J774, our results suggest that these aromatic compounds might constitute potential as leader molecules in the development of more effective and less toxic analogs that could have considerable implications for future therapies of onychomycosis.

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“…These compounds are intriguing as they are not only active on their own, they are also often metabolized to a range of other RSeS, such as selenols, diselenides and seleninic acids. [33][34][35][36][37] Once again, such organoselenium compounds are not "exotic" and -either directly or as metabolites -play significant roles in Biology. 38 Although aromatic selenocyanates so far have mostly been studied when attached to some other "bioactive" scaffolds which may have influenced or even dominated their biological activity, they have also been reported to exhibit leishmanicidal activity.…”

Section: -32mentioning

confidence: 99%