Ethanolamine plasmalogen and cholesterol reduce the total membrane oxidizability measured by the oxygen uptake method

To investigate the effects of ethanolamine plasmalogen, phosphatidylethanolamine, cholesterol, and alpha-tocopherol on the oxidizability of membranes, various large unilamellar vesicles (LUVs) including these lipids and antioxidant were examined for their total membrane oxidizabilities, evaluated as R(p)/R(i)(1/2) value (where R(p) is rate of oxygen consumption and R(i)(1/2) is the square root of rate of chain initiation) by the oxygen uptake method with water-soluble radical initiator and inhibitor. Incorporation of bovine brain ethanolamine plasmalogen (BBEP) into vesicles as well as cholesterol led to lower the total membrane oxidizability dose-dependently. The effect of BBEP was more efficient in the presence of cholesterol in vesicles. On the other hand, diacyl counterpart, egg yolk phosphatidylethanolamine, and a typical radical scavenger, alpha-tocopherol, had no effect on the membrane oxidizability. Alpha-tocopherol only prolonged an induction period dose-dependently in the present oxidizing system, suggesting a novel antioxidant mechanism of ethanolamine plasmalogens besides the action of scavenging radicals.     

1,2,3-Triazole Derivatives as an Emerging Scaffold for Antifungal Drug Development against Candida albicans: A Comprehensive Review

Candida infections are most prominent among fungal infections majorly target immunocompromised and hospitalized patients and cause significant morbidity and mortality. Candida albicans is the notorious and most prevalent among all pathogenic Candida strains. Its emerging resistance toward available antifungal agents making it hard to tackle and emerging as global healthcare emergency. Simultaneously, 1,2,3-triazole nucleus is a privileged scaffold that is gaining importance in antifungal drug development due to being a prominent bioactive linker and isostere of triazole based antifungal class core 1,2,4-triazole. Numerous reports have been updated in scientific literature in last few decades related to utilization of 1,2,3-triazole nucleus in antifungal drug development against Candida albicans. Present review will shed light on various preclinical studies focused on development of 1,2,3-triazole derivatives targeting Candida albicans along with brief highlight on clinical trials and newly approved drugs. Structure-activity relationship has been precisely discussed for each architect along with future perspective that will help medicinal chemists in design and development of potent antifungal agents for tackling infections derived from Candida albicans.     

Influence of the triazole growth retardant BAS 111..W on phytohormone levels in senescing intact pods of oilseed rape

Foliar treatment of oilseed rape plants (Brassica napus L.ssp. napus cv. Linetta) with the growth retardant BAS 111..W at the 5th leaf stage delayed pod senescence during early maturation. Changes of immunoreactive cytokinin- and abscisic acid (ABA)- like substances and of the ethylene precursor 1-aminocyclo-propane-1-carboxylic acid (ACC) and its malonyl-conjugate (MACC) were determined in intact whole pods. When compared with control plants, higher levels of total chlorophyll correlated with four-fold and three-fold increases of trans-zeatin riboside- and dihydrozeatin riboside-type cytokinins, respectively, in the pods of plants treated with 0.25 mg BAS 111..W per plant. Isopentenyladenosine-type cytokinins and ACC and MACC contents remained virtually unchanged, whereas ABA levels dropped considerably below those of controls (60% reduction). However, when analysed at late pod maturity, BAS 111..W treatment no longer affected the total chlorophyll content, or the levels of cytokinins, ABA, ACC and MACC. We hypothesize that the retardant-induced changes in the hormonal status of the pods, favouring the senescence-delaying cytokinins as opposed to abscisic acid, could contribute to the developmental delay.     

A single 8-hydroxyquinoline-appended bile acid fluorescent probe obtained by click chemistry for solvent-dependent and distinguishable sensing of zinc(II) and cadmium(II)

Construction of fluorescent probes for zinc ion (Zn²⁺) and cadmium ion (Cd²⁺) is significant for the safety of humans. However, the discriminating recognition of Zn²⁺ and Cd²⁺ by a single probe remains challenging owing to their similar properties. Herein, a novel deoxycholic acid derivative containing 8-hydroxyquinoline fluorophore has been facilely synthesized through click chemistry to form a clamp-like probe. Using its perfect bonding cavity from 1,2,3-triazole and quinoline, this molecule showed favorable solvent-dependent fluorescent responses and distinguished Zn²⁺ and Cd²⁺ in different solvents. In ethanol aqueous solution, it displayed good selectivity and ratiometric fluorescence to Zn²⁺ with 30 nm spectroscopic red-shifts. In acetonitrile aqueous solution, it exhibited good selectivity and ratiometric fluorescence to Cd²⁺ with 18 nm spectroscopic red-shifts. Moreover, the unique microstructural features of the probe in assembly were used to reflect its recognition processes. Due to its merits of low detection limit and instant response time, the probe was utilized for sensing Zn²⁺ and Cd²⁺ in water, beer and urine with high accuracy. Meanwhile, this probe served as a handy tool and was employed to obtain inexpensive test strips for the prompt and semiqualitative analysis of Zn²⁺ and Cd²⁺ with the naked eye.     

Green leaf area decline of wheat flag leaves: the influence of fungicides and relationships with mean grain weight and grain yield

A modified Gompertz model was derived to describe the fractional decline in green area of wheat flag leaves in field experiments where green leaf area at time t=100exp[‐exp(‐k(t‐m))]. Curves fitted over time to visual assessments of green leaf area (% of total leaf area) throughout flag leaf life accounted for more than 98% of variation in 45 of 48 wheat cultivar × fungicide treatment (+/?) comparisons. This data set spanned 17 yr and therefore included cultivars of contrasting parentage and age. In the absence of fungicide, green leaf area decline was associated with drought or infection with a number of foliar pathogens including Septoria tritici (sexual stage Mycospherella graminicola), Erysiphe graminis and Puccinia striiformis. Fungicides applied to the flag leaf included propiconazole, propiconazole plus tridemorph, flusilazole or azoxystrobin. Fungicide effects on m (i.e. time to 37% green area) were closely related to fungicide effects (% of untreated) on mean grain weight (variation accounted for (VAF) = 80%) and grain yield (VAF = 85%).     

Antibacterial and antifungal metal based triazole Schiff bases

A new series of four biologically active triazole derived Schiff base ligands (L¹–L⁴) and their cobalt(II), nickel(II), copper(II) and zinc(II) complexes (1–16) have been synthesized and characterized. The ligands were prepared by the condensation reaction of 3-amino-5-methylthio-1H-1,2,4-triazole with chloro-, bromo- and nitro-substituted 2-hydroxybenzaldehyde in an equimolar ratio. The antibacterial and antifungal bioactivity data showed the metal(II) complexes to be more potent antibacterial and antifungal than the parent Schiff bases against one or more bacterial and fungal species.     

Molecular mechanism of deactivation of C. antarctica lipase B by methanol

The catalytic activity of Candida antarctica lipase B upon alcoholysis of a constant concentration of 15.2% vinyl acetate (vol/vol) and varying concentrations of methanol (0.7–60%) in toluene was determined experimentally by measuring the initial reaction velocity. The molecular mechanism of the deactivation of the enzyme by methanol was investigated by fitting the experimental data to a kinetic model and by molecular dynamics simulations of C. antarctica lipase B in toluene–methanol–water mixtures.     

Synthesis of quinoline coupled [1,2,3]-triazoles as a promising class of anti-tuberculosis agents

A series of quinoline coupled 1,2,3-triazoles compounds have been synthesized by ‘click chemistry’ from azidomethyl quinoline with different alkynes. The efficiency and fidelity of the Cu(I)-catalyzed azide–alkyne reaction are substantiated by good yields and exclusive formation of the expected 1,4-disubstituted triazole product. All the synthesized compounds were screened for anti-tubercular activity against Mycobacterium tuberculosis H37Rv by luciferase reporter phage (LRP) assay. Quinoline coupled triazole sugar hybrid, 20 is the most potent compound in the series with 76.41% and 78.37% reduction calculated based on percentage reduction in Relative Light Units at 5 and 25 μg/mL, respectively.     

A triazole‐based fluorescence probe for detecting Hg2+ ions and its biological application

A new compound, ethyl 5‐phenyl‐2‐(p‐tolyl)‐2H‐1,2,3‐triazole‐4‐carboxylate was successfully introduced and synthesized as a novel rhodamine B derivative named REPPC, and characterized by ¹H nuclear magnetic resonance (NMR), ¹³C NMR, and high resolution mass spectrometry (HRMS). It showed an obvious fluorescence and UV–visible light absorption enhancement towards Hg²⁺ ion without interference from common metal ions in N,N‐dimethylformamide–H₂O (pH 7.4). The spirolactam ring moiety of rhodamine in REPPC was converted to the open‐ring form generating a 1:1 complex with the intervention of a mercury ion, verified by electrospray ionization‐mass spectroscopy testing and density functional theory calculation. REPPC was used to visualize the level of mercury ions in living HeLa cells with encouraging results.     

Trypanocidal activity of peptidyl vinyl ester derivatives selective for inhibition of mammalian proteasome trypsin-like activity

Nine vinyl ester tripeptides selective for inhibition of mammalian proteasome trypsin-like activity were tested for in vitro activity against Trypanosoma brucei. Interestingly, two compounds showed trypanocidal activity in the low micromolar range without displaying cytotoxicity against human cells. However, the compounds did not inhibit the trypsin-like activity of the trypanosome proteasome although their effect correlates with inactivation of the chymotrypsin-like activity. This finding shows that the inhibitor sensitivities between mammalian and trypanosome proteasome are distinct. This difference may be exploited for rational anti-trypanosomal drug development.