Dimeric 1,4-benzoquinone derivatives and a resorcinol derivative from Ardisia gigantifolia

Naturally occurring dimeric 1,4-benzoquinone derivatives, belamcandaquinones F, G, H, and I, as well as one resorcinol derivative and four known compounds, were isolated from rhizomes of Ardisia gigantifolia. Their structures were established by means of spectroscopic analyses. All compounds were tested against cell lines PC-3, EMT6, A549, Hela, RM-1, and SGC7901 for cytotoxicity in vitro. In comparison with cisplatin, compounds 5 and 6 showed a strong cytotoxicity with IC₅₀ values less than 30 μM for most cell lines tested.     

Soybean peroxidase-catalyzed removal of phenylenediamines and benzenediols from water

Crude soybean peroxidase (SBP), isolated from soybean seed coats (hulls), catalyzes the oxidative polymerization of hazardous aqueous phenylenediamines and benzenediols in the presence of hydrogen peroxide. Experiments were conducted to investigate the optimum operating conditions including pH, hydrogen peroxide-to-substrate concentration ratio and the minimum SBP concentration required to achieve at least 95% conversion of these pollutants in synthetic wastewaters. The substrate conversion and hydrogen peroxide consumption were monitored over the period of the reactions. Polyethylene glycol (PEG) was ineffective as an additive in enhancing the conversion efficiency. The enzymatically generated polymeric products from phenylenediamines could be removed with the aid of a surfactant, sodium dodecyl sulfate (SDS), whereas the polyvalent metal cation salt, aluminum sulfate (alum), was able to remove the products from benzenediols, except hydroquinone. Enzyme-catalyzed polymerization with SBP and subsequent removal of the polymeric products generated can provide an alternative means to the conventional methods for treating many aromatic wastewater pollutants, including the title compounds.     

Discovery of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl)acetates as potent Hsp90 inhibitors with selectivity over TRAP1

As the most abundant heat shock protein (HSP), Hsp90 is actively involved in tumor cell growth and various responses to anti-carcinogenic stress. Hsp90 has thus emerged as a potential drug target. A structure-based drug design approach was applied to develop novel resorcinolyltriazole derivatives as Hsp90 inhibitors. Structure-activity relationships (SARs) and molecular docking were investigated to provide a rationale for binding affinity and paralog selectivity. Click chemistry between iodoethynylresorcinol and an azido derivative was used to synthesize a new family of 2-((4-resorcinolyl)-5-aryl-1,2,3-triazol-1-yl) acetates that exhibited Hsp90 binding affinities of 40–100 nM (IC₅₀). Among the synthesized molecules, the triazole alkyl acetates displayed the highest Hsp90 binding affinities. Their potency against Hsp90 was over 100-fold stronger than against TRAP1 and 1–3-fold stronger than against Grp94. In particular, compounds 18, 19, and 30 had Hsp90 inhibitory activities of ~45 nM (IC₅₀) and they displayed over 350-fold selectivity for Hsp90 over TRAP1.     

Anaerobic metabolism of resorcyclic acids (m-dihydroxybenzoic acids) and resorcinol (1,3-benzenediol) in a fermenting and in a denitrifying bacterium

The anaerobic metabolism of 2,4- and 2,6-dihydroxybenzoic acid (beta- and gamma-resorcyclic acid) and 1,3-benzenediol (resorcinol) was investigated in a fermenting coculture of a Clostridium sp. with a Campylobacter sp. (Tschech A and Schink B (1985) Arch Microbiol 143: 52–59) and in a newly isolated denitrifying gram-negative bacterium. The enzymes of this pathway were searched for and partly characterized in vitro. It is shown that resorcyclic acids are decarboxylated in both organisms by specific enzymes, 2,4- or 2,6-dihydroxybenzoic acid decarboxylase. In the fermenting bacterium, the aromatic product, 1,3-benzenediol, is reduced by 1,3-benzenediol (resorcinol) reductase to the non-aromatic 1,3-cyclohexanedione; the novel enzyme which catalyzes the two-electron-reduction of the aromatic nucleus is oxygen-sensitive and uses reduced methyl viologen as artificial electron donor. The cyclic dione is then hydrolytically cleaved to 5-oxocaproic acid by 1,3-cyclohexanedione hydrolase. The denitrifying bacterium did not metabolize 1,3-cyclohexanedione, and the enzymes metabolizing 1,3-benzenediol or 1,3-cyclohexanedione were not detected. It is concluded that two different pathways of anaerobic 1,3-benzenediol metabolism exist.