Effect of triazole‐tryptophan hybrid on the conformation stability of bovine serum albumin

The effect of a potent antimicrobial compound bearing 1,2,3‐triazole core and a tryptophan tail, triazole‐tryptophan hybrid (TTH), with bovine serum albumin (BSA) have been explored using various spectroscopic and molecular docking methods. Studies revealed that TTH strongly quenches the intrinsic fluorophore of BSA by a static quenching mechanism. Time‐resolved fluorescence spectra further confirmed the involvement of static quenching for TTH–BSA system. The calculated thermodynamic parameters; ΔH, ΔS, and ΔG showed that the binding process was spontaneous, exothermic and entropy driven. Synchronous fluorescence, three‐dimensional (3D) fluorescence and circular dichroism data revealed that TTH induces the structural alteration in BSA and enhances its stability. In silico study of TTH–BSA system showed that it binds with BSA at the site I of subdomain IIA. Both the experimental and in silico study showed that the hydrophobic and electrostatic interactions play a major role in TTH–BSA binding.     

Control of the migratory aptitudes of vinyl and aryl ligands in ruthenium(II) complexes

Complexes Ru(CO)₂ (CH=CHR) (C₆H₄X-4)L₂ (R=^tBu, Ph, OEt; X=H, Cl, OMe; L=PMe₃, PMe₂Ph, P(OMe)₂Ph) in which the two phosphorus ligands are mutually cis (isomer 1) react readily with ligands ^tBuNC, CO and P(OMe)₃ to give complexes in which one of the organic ligands has migrated onto a carbonyl ligand. Vinyl migration products (5) retain the mutually cis geometry of the phosphorus ligands, and are unstable: one of the decomposition products is the ketone RCH=CHC(O)C₆H₄X-4. Phenyl migration products (4) are stable and have the phosphorus ligands in mutually trans positions; an X-ray crystal structure of Ru(CO) (CN^tBu) {C(O)Ph} (CH=CHPh) (PMe₂Ph)₂ was obtained. In both cases, the incoming ligand enters trans to the newly formed acyl ligand. Vinyl migration is favoured over aryl migration by electron-donating substituents on the vinyl ligand, electron-withdrawing substituents on the aryl ligand, good σ-donor phosphorus ligands and use of ^tBuNC as the incoming ligand. The rate of phenyl migration in Ru(CO)₂(CH=CHPh)Ph(PMe₂Ph)₂ is independent of ^tBuNC concentration: k=1.5 × 10⁻³ s⁻¹ at 20°C. Isomer 3 of complexes Ru(CO)₂(CH=CHR) (C₆H₄X-4)L₂ in which the phosphorus ligands are mutually trans is much less reactive towards migration reactions. The reactivity of isomer 1 is attributed to the steric strain of two mutually cis phosphorus ligands.     

1,5-Disubstituted 1,2,3-triazole linked disaccharides: Metal-free syntheses and screening of a new class of ribonuclease A inhibitors

1,5-Regioisomeric triazole linked disaccharides have been synthesized and screened for their inhibitory properties against ribonuclease A (RNase A). The angular constraint-driven ‘crescent shaped’ inhibitors accommodated themselves into the enzyme active site. An improved enzyme inhibition was observed with increased H-bonding ability of polar functional groups in the modified disaccharides. In this series, introduction of two carboxyl groups in the furanose rings elicited the best result with an inhibition constant of 50?±?3?µM. This is the first ever report on the use of disaccharides as RNase A inhibitors.     

Changes in root-shoot ratio and ion uptake of maize (Zea mays L.) from soil as influenced by a plant growth regulator

A pot experiment with maize cv. Limac was conducted to investigate the influence of BAS 110.. W, a plant growth regulator (PGR), on root and shoot development and nutrient uptake. The PGR was applied via the soil with 0, 5, 10, 20, and 40 mg a.i. per pot. Shoot dry matter production was reduced to a higher degree than root length, resulting in a higher root-shoot ratio (RSR) of the treated plants. Shoots of treated plants contained higher concentrations of N, P, Ca, Mg, and unchanged K concentrations. The alterations in concentration could be explained by the changes in RSR induced by the plant growth retardant. The effect was strongest with P (+40%) which was limited by soil supply. N, Ca, and Mgconcentrations were positively influenced (+20%), there was no increase for Kvs RSR.     

Discovery of a new class of cinnamyl-triazole as potent and selective inhibitors of aromatase (cytochrome P450 19A1)

Synthesis of a novel class of natural product inspired cinnamyl-containing 1,4,5-triazole and the potent inhibition of human aromatase (CYP 450 19A1) by select members is described. Structure–activity data generated provides insights into the requirements for potency particularly the inclusion of an aryl bromide or chloride residue as a keto-bioisostere.     

Synthesis of β-Hydroxyphosphonate and 1,2-Dihydroxy Acyclic Nucleoside Analogs via 1,3-Dipolar Cycloaddition Strategy

A convenient synthetic approach toward nucleoside analogs where β-hydroxyphosphonate- or 1,2-dihydroxy units are connected to the nucleic acid base through a triazole spacer is discussed.     

Recent advances in chlorophyll biosynthesis

The importance of chlorophyll (Chl) to the process of photosynthesis is obvious, and there is clear evidence that the regulation of Chl biosynthesis has a significant role in the regulation of assembly of the photosynthetic apparatus. The understanding of Chl biosynthesis has rapidly advanced in recent years. The identification of genetic loci associated with each of the biochemical steps has been accompanied by a greater appreciation of the role of Chl biosynthesis intermediates in intracellular signaling. The purpose of this review is to provide a source of information for all the steps in Chl and bacteriochlorophyll a biosynthesis, with an emphasis on steps that are believed to be key regulation points.     

Synthesis and biological properties of C-terminal vinyl ketone pseudotripeptides

The ubiquitin-proteasome pathway responsible for the turnover of many cellular proteins represents an attractive target in the development of new drug therapies: In particular, modulation of the proteasome activity by specific inhibitors may represent a useful tool for the treatment of tumours. Here, we report synthesis and activity of a new series of oligopseudopeptide analogues bearing a vinyl ketone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the µM range of the trypsin-like (T-L) active site of the proteasome.     

Analogs design,synthesis and biological evaluation of peptidomimetics with potential anti-HCV activity

Two series of peptidomimetics were designed, prepared and evaluated for their anti-HCV activity. One series possesses a C-terminal carboxylate functionality. In the other series, the electrophilic vinyl sulfonate moiety was introduced as a novel class of HCV NS3/4A protease inhibitors. In vitro based studies were then performed to evaluate the efficacies of the inhibitors using Human hepatoma cells, with the vinyl sulfonate ester (10) in particular, found to have highly potent anti-HCV activity with an EC₅₀ = 0.296 μM. Finally, molecular modeling studies were performed through docking of the synthesized compounds in the HCV NS3/4A protease active site to assess their binding modes with the enzyme and gain further insight into their structure–activity relationships.     

Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

Aims: Determine whether certain, natural phenolic compounds enhance activity of commercial antifungal drugs against yeast strains of Candida and Cryptococcus neoformans. Methods and Results: Twelve natural phenolics were examined for fungicidal activity against nine reference strains of Candida and one of C. neoformans. Six compounds were selected for synergistic enhancement of antifungal drugs, amphotericin B (AMB), fluconazole (FLU) and itraconazole (ITR). Matrix assays of phenolic and drug combinations conducted against one reference strain, each, of Candida albicans and C. neoformans showed cinnamic and benzoic acids, thymol, and 2,3‐ and 2,5‐dihydroxybenzaldehydes (‐DBA) had synergistic interactions depending upon drug and yeast strain. 2,5‐DBA was synergistic with almost all drug and strain combinations. Thymol was synergistic with all drugs against Ca. albicans and with AMB in C. neoformans. Combinations of benzoic acid or thymol with ITR showed highest synergistic activity. Of 36 combinations of natural product and drug tested, none were antagonistic. Conclusions: Relatively nontoxic natural products can synergistically enhance antifungal drug activity, in vitro. Significance and Impact of the Study: This is a proof‐of‐concept, having clinical implications. Natural chemosensitizing agents could lower dosages needed for effective chemotherapy of invasive mycoses. Further studies against clinical yeast strains and use of animal models are warranted.