Antifungal Activity of Tetrasulfanes against Botrytis cinerea

Abstract

Various natural polysulfanes (RS x R', x ≥ 3, R ≠ H), such as diallyltrisulfide and diallyltetrasulfide from garlic, are mostly harmless to humans, higher animals and plants, yet highly active against diverse microbes, including several fungi. Such natural organic sulfur compounds (OSCs) possess considerable practical potential against a wide range of agricultural pests. Unfortunately, their use is often hampered due to the inherently offensive smell, chemical instability and low water solubility. However, since the biological activity of polysulfanes is primarily based on their unique sulfur-sulfur motif, it is possible to preserve this motif and to modify the side-chain(s). Ultimately, such changes result in synthetic polysulfanes which retain or even exceed the activity of their natural analogues, and also show improved physico-chemical properties. The resulting acid-, ether-and ester-based tetrasulfanes synthesized as part of this study are odorless and highly active against the grey mold fungus Botrytis cinerea. Some, but not all, of the synthetic polysulfanes are recognized by an active fungal efflux mechanism mediated by the ABC transporter AtrB. Remarkably, some of them even induce transcription of the AtrB-encoding gene, mediated by transcription factor Mrr1. Taken together, the activity of synthetic polysulfanes against B. cinerea, combined with a likely low ecotoxicity of such sulfur compounds, bodes well for possible future applications against this and eventually other agronomically important plant pathogens.

Synthesis and antiproliferative properties of a new ceramide analog of varacin

“…For ceramide 1 , we suggest that S 3 is the reactive intermediate underlying bioactivity. Reactive sulfur species (Sato et al, 1987; Lee et al, 2002; Münchberg et al, 2007; Anwar, 2008; Nielsen et al, 2011; Czepukojc et al, 2013a; Czepukojc et al, 2013b) such as diatomic sulfur, S 2 , can arise in other polysulfanes (Abu-Yousef and Harpp, 1998; Abu-Yousef, 2006; Zysman-Colman and Harpp, 2007; Rys et al, 2008; Startsev et al, 2015). Relatedly, the antiproliferative activity of Bittman’s ceramide-disulfane conjugate, N -(4′,5′-dithiaheptanoyl)- D -erythro-ceramide, was correlated to a reduction in cellular glutathione (GSH) levels in cancer cells (Bittman et al, 2007).…”

A scent of therapy: Synthetic polysulfanes with improved physico-chemical properties induce apoptosis in human cancer cells

“…As part of the synthetic procedures, the classical procedure of Derbesy and Harpp (5) and of Milligan et al (4), respectively, have been modified in order to produce the relevant asymmetric polysulfanes (6,7). The analytical data obtained for both compounds is in agreement with their structure and indicate a purity of ≥94% for ATSEE and ≥95% for ATTSB (see Materials and methods).…”

“…A reduction in cell number can be due to the induction of apoptosis, a process studied extensively for many natural organic sulfur compounds (6,13,16,18). To investigate this possibility, we treated HCT116 cells with 50 µm ATTSB or 50 µM ATSEE.…”

“…The chemical synthesis provides these compounds in high quantities and with great purity. Indeed, our own group has used and recently refined these traditional synthetic procedures in order to synthesize a range of new symmetric and asymmetric polysulfanes, often with especially designed properties (6,7). The availability of such pure compounds in good yields has also stimulated the analysis of various biological activities of individual compounds, especially, but not exclusively, in the context of cancer research (8,9).…”

Special Issue: Redox Active Natural Products and Their Interaction with Cellular Signalling Pathways

“…Such targets for redox modulation include, for instance, aggressively proliferating cells, but also pathogenic organisms affecting humans, animals and plants. Not surprisingly, allicin and related polysulfanes are currently under discussion in the context of cancer, inflammatory and infectious diseases and systemic sclerosis, whilst mixtures of such reactive sulfur species (RSS) are already used as green pesticides in agriculture [1,3,4,20,21,22,23,24,25,26].…”