Synthesis and Structure?Activity Relationships of Antifungal Crassinervic Acid Analogs

A series of analogs of the natural antifungal compound crassinervic acid, a constituent of Piper crassinervium, were synthesized to gain insight into the most relevant structural features affecting the activity of the parent molecule. Most compounds were prepared by aldol reaction of methyl 3‐acetyl‐4‐hydroxybenzoate with a series of ketones, followed by reduction, hydrolysis, and oxidation. The antifungal activities of crassinervic acid and its analogs was assessed against Cladosporium cladosporioides by using the method of bioautography. The bioassay results allowed us to depict structure? activity relationships for this class of compounds.     

Defensive Sesquiterpenes from Senecio candidans and S. magellanicus,and Their Structure?Activity Relationships

Eleven eremophilanolides, 1 – 3 and 6 – 13 , and two eremophilanes, 24 and 25 , were isolated from Senecio candidans and S. magellanicus from the Magallanes Region (Chile). Compounds 2, 3, 9 , and 10 have not been previously reported as natural products. Their structures were established by NMR spectroscopic analysis and chemical transformations. The X‐ray analysis of compounds 11, 13 , and 17 were also performed. Different semisynthetic analogs from eremophilanolide 11 were generated to carry out a structure? activity relationship study. Their possible plant defensive role was tested against herbivorous insects (Spodoptera littoralis, Rhopalosiphum padi, and Myzus persicae) and plants (Lactuca sativa). Additionally, their effects on insect (Sf9) and mammalian (CHO) cell lines were tested.     

Aggregation‐Induced Emission of 1,8‐Naphthalimide?Casein Micelle: Investigation by Synchronous Spectrographic Method

A novel 1,8‐naphthalimide probe 1 , bearing two acetic‐acid moieties was synthesized. The acetic‐acid groups, docked into the sub‐domains of casein micelle and bound with tryptophan residues, and the 1,8‐naphthalimide chromophore adsorbed on the surface of casein micelle, forming a supermolecule, 1 ? casein micelle, which exhibited the aggregation‐induced synchronous emission (AISE) characters. The effect of pH on the intensity of supermolecule was investigated, and the result indicated that the emission enhancement was mainly due to the 1,8‐naphthalimide chromophore aggregated onto the casein micelle. Based on AISE, a novel casein quantification method was developed, which exhibited a good linear range of 0.05–10.0 μg ml^?1 and 0.07–9.5 μg ml^?1 with the detection limits of 2.8 and 3.0 ng ml^?1. The effects of metal ions and pH on the system of 1 ? casein micelle were investigated. The proposed method was applied to determine casein in milk samples, and the results were in good agreement with the result of the Biuret method.     

Studies on Chemical‐Structure Modification and Structure?Activity Relationship of Gambogic Acid Derivatives at Carbon(34)

Gambogic acid (GA), a natural product, was identified as a promising antitumor agent. To further explore the structure? activity relationship of GA and discover novel GA derivatives as antitumor agents, 19 novel GA derivatives modified at C(34) were synthesized and evaluated against A549, BGC‐823, U251, HepG2, and MB‐231 cancer cell lines by cellular assays. Among them, 15 compounds were found to be more potent than GA against some cancer cell lines. Notably, compound 3 possessed potent inhibitory activities against five cell lines with IC₅₀ values ranging between 0.24 and 1.09 μM . Compounds 9 and 18 were seven to eightfold more active than GA against A549 cell line. Chemical modification at C(34) of GA by introducing of hydrophilic aliphatic amines resulted in increased activity and improved drug‐like properties. These findings will enhance our understanding of the SAR of GA and can lead to the discovery of novel GA derivatives as potential antitumor agents.     

GC (Guanine‐Cytosine)‐Selective DNA‐Binding and Antitumor Activity of a Quercetin?Manganese(II) Complex

The DNA binding and cleavage properties of quercetin? manganese(II) complexes have been studied, but little attention has been devoted to the relationship between the antitumor activity of these complexes and the DNA‐binding properties. Here, the DNA binding properties of the quercetin? manganese(II) complex [Mn(Que)₂(H₂O)₂] were studied using UV/VIS and fluorescence spectroscopy and viscosity measurements. The results indicate that the complex was preferentially bound to DNA in the GC (guanine? cytosine)‐rich regions via an intercalative mode. Furthermore, the cytotoxicity experiments confirmed its apoptosis‐inducing activity. We also demonstrated that the levels of survivin protein expression in HepG2 cells decreased and that the relative activity of caspase‐3 significantly increased after treatment with the complex. Hence, our results suggest that the antitumor activity of the [Mn(Que)₂(H₂O)₂] complex might be related to its intercalation into DNA and its DNA‐binding selectivity.     

Structure?Activity Relationship of Polypyridyl Ruthenium(II) Complexes as DNA Intercalators,DNA Photocleavage Reagents,and DNA Topoisomerase and RNA Polymerase Inhibitors

To investigate the relationship between the molecular structure and biological activity of polypyridyl Ru^II complexes, such as DNA binding, photocleavage ability, and DNA topoisomerase and RNA polymerase inhibition, six new [Ru(bpy)₂(dppz)]²⁺ (bpy=2,2′‐bipyridine; dppz=dipyrido[3,2‐a:2,′,3′‐c]phenazine) analogs have been synthesized and characterized by means of ¹H‐NMR spectroscopy, mass spectrometry, and elemental analysis. Interestingly, the biological properties of these complexes have been identified to be quite different via a series of experimental methods, such as spectral titration, DNA thermal denaturation, viscosity, and gel electrophoresis. To explain the experimental regularity and reveal the underlying mechanism of biological activity, the properties of energy levels and population of frontier molecular orbitals and excited‐state transitions of these complexes have been studied by density‐functional theory (DFT) and time‐depended DFT (TDDFT) calculations. The results suggest that DNA intercalative ligands with better planarity, greater hydrophobicity, and less steric hindrance are beneficial to the DNA intercalation and enzymatic inhibition of their complexes.     

Synthesis,Characterization, and DNA‐Binding and ‐Cleavage Properties of Dinuclear CuII?Salophen/Salen Complexes

Dinuclear Cu^II complexes, [Cu₂(salophen)₂] ( 1 ) and [Cu₂(salen)₂] ( 2 ), with Schiff bases derived from salicylaldehyde and o‐phenylenediamine (ophen) or ethylenediamine (en) were synthesized and characterized. They exhibit square‐planar geometry with CuN₂O₂ coordination, where the dianionic Schiff base acts as a tetradentate N₂O₂ donor ligand. Calf thymus (CT)‐DNA Binding studies revealed that the complexes possess good binding propensities (K_b=3.13×10⁵ for 1 and K_b=2.99×10⁵ M ⁻¹ for 2 ). They show good DNA‐cleavage abilities under oxidative and hydrolytic conditions. Complex 1 binds and cleaves DNA more efficiently as compared to 2 due to the presence of an extended aromatic phenyl ring which might be involved in an additional stacking interaction with DNA bases. From the kinetic experiments, hydrolytic DNA‐cleavage rate constants were determined as 1.54 for 1 and 0.72 h⁻¹ for 2 . The nuclease activities of 1 and 2 are significant, giving rise to (2.03–2.88)×10⁷‐fold rate enhancement compared to non‐catalyzed DNA cleavage.     

In Situ Revealing the Electroactivity of P?O and P?C Bonds in Hard Carbon for High‐Capacity and Long‐Life Li/K‐Ion Batteries

The low capacity and unsatisfactory rate capability of hard carbon still restricts its practical application for Li/K‐ion batteries. Herein, a low‐cost and large‐scale method is developed to fabricate phosphorus‐doped hard carbon (PHC‐700) by crosslinking phosphoric acid and epoxy resin and followed by annealing at 700 °C. H₃PO₄ acts not only as a crosslinker to solidify epoxy resin for promoting the degree of graphitization and lowering the specific surface area, but also as phosphorus source for forming P? C and P? O bonds, thus providing more active sites for Li/K storage. As a result, the PHC‐700 electrode delivers a highly reversible capacity of 1294.8 mA h g^?1 at 0.1 A g^?1 and a capacity of 214 mA h g^?1 after 10 000 cycles at 10 A g^?1. As for potassium‐ion batteries, PHC‐700 exhibits a reversible capacity of 381.9 mA h g^?1 at 0.1 A g^?1 and a capacity of 260 mA h g^?1 after 1000 cycles at 0.2 A g^?1. In situ Raman and in situ NMR measurements reveal that the P‐containing bonds can enhance the adsorption to alkali metal ions, and the P? C bond can participate in electrochemical redox reaction by forming Li_x PC_y . Additionally, P‐doped hard carbon shows better structural/interfacial stability for improved long‐term cycling stability.     

Oxidative DNA Damage Induced by a Copper(II)?1,10‐Phenanthroline?L‐Serine Complex in the Presence of Rutin

The capacity of the ternary complex copper(II)? 1,10‐phenanthroline? L ‐serine ([Cu? Phen? Ser]) to induce double‐strand scission of DNA was explored by agarose‐gel electrophoresis. It was found that the complex exhibited remarkable activity to damage DNA in the presence of rutin. Analysis of the UV and fluorescence spectra clearly demonstrated that the complex was bound to DNA by intercalation. Further, the occurrence of 8‐hydroxydeoxyguanosine (8‐OHdG), a biomarker of oxidative DNA damage, after the treatment of DNA by the complex in presence of rutin was evidenced by an electrochemical method. Finally, the mechanism of oxidative damage to double‐stranded DNA by the [Cu? Phen? Ser] complex in the presence of rutin was discussed.     

Cyclopaldic Acid,Seiridin, and Sphaeropsidin A as Fungal Phytotoxins,and Larvicidal and Biting Deterrents against Aedes aegypti (Diptera: Culicidae): Structure?Activity Relationships

Aedes aegypti L. is the major vector of the arboviruses responsible for dengue fever, one of the most devastating human diseases. From a preliminary screening of fungal phytotoxins, cyclopaldic acid ( 1 ), seiridin ( 2 ), sphaeropsidin A ( 4 ), and papyracillic acid ( 5 ) were evaluated for their biting deterrent and larvicidal activities against Ae. aegypti L. Because compounds 1, 2, 4 , and 5 exhibited mosquito biting deterrent activities and 1 and 4 demonstrated larvicidal activities, further structure? activity relationship studies were initiated on these toxins. In biting‐deterrence bioassays, 1, 2, 4 , and 5 , 3,8‐didansylhydrazone of cyclopaldic acid, 1F , 5‐azidopentanoate of cyclopaldic acid A, 1G , the reduced derivative of cyclopaldic acid, 1 H , isoseiridin ( 3 ), 2′‐O‐acetylseiridin ( 2A ), 2′‐oxoseiridin ( 2C ), 6‐O‐acetylsphaeropsidin A ( 4A ), 8,14‐methylensphaeropsidin A methyl ester ( 4B ), and sphaeropsidin B ( 4C ) showed activities higher than the solvent control. Sphaeropsidin B ( 4C ) was the most active compound followed by 2A , while the other compounds were less active. Biting‐deterrence activity of compound 4C was statistically similar to DEET. In the larvicidal screening bioassays, only compounds 1 and 4 demonstrated larvicidal activities. Based on LD₅₀ values, compound 4 (LD₅₀ 36.8 ppm) was significantly more active than compound 1 (LD₅₀ 58.2 ppm). However, the activity of these compounds was significantly lower than permethrin.     

Studies on Chemical Structure Modification and Structure?Activity Relationship of Derivatives of Gambogic Acid at C(39)

The natural product gambogic acid exhibits high potency in inhibiting cancer cell lines. Rational medicinal modifications on gambogic acid will improve its physicochemical properties and drug‐like characters. To investigate the structure? activity relationship of gambogic acid and also to find rational modification position on its chemical skeleton, we designed, synthesized, and characterized 16 derivatives of gambogic acid that were modified at C(39). The structure? activity relationships (SARs) were discussed. The anti‐proliferation data were accquired through MTT (=3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide) assays of A549, BGC823, U251, HepG2, and MDA‐MB‐231 cancer cell lines. Most of the synthesized compounds showed strong inhibitory effects. The SAR study revealed that derivatives with aliphatic amino moieties at C(39) were more potent than those with other substituents. The C(39) position can undergo different kinds of chemical modifications without leading to loss of activity. Compounds 4 and 6 can serve as potential lead compounds for further development of new anticancer drugs.     

A Novel Monoterpene?Stilbene Adduct with a 4,4‐Dimethyl‐2,3‐diphenylchromane Skeleton from Artocarpus xanthocarpus

Artoxanthochromane ( 1 ), a Diels? Alder‐type conjugation product of 4‐isopropenylresorcinol and oxyresveratrol, was isolated from the heartwood of Artocarpus xanthocarpus and characterized. The structure of 1 was elucidated as 2‐(2,4‐dihydroxyphenyl)‐3‐(3,5‐dihydroxyphenyl)‐7‐hydroxy‐4,4‐dimethylchromane by 1D‐ and 2D‐NMR spectroscopy, and other spectral evidences. A plausible metabolic mechanism was proposed to illustrate the biosynthetic pathway of artoxanthochromane. This compound exhibited mild mushroom tyrosinase inhibitory, and weak free radical‐scavenging activities on ABTS^+. and superoxide anion (O ) free radicals.     

Updated Metal Compounds (MOFs, ?S, ?OH, ?N, ?C) Used as Cathode Materials for Lithium–Sulfur Batteries

Lithium–sulfur (Li–S) batteries have the potential to be as efficient and as widespread as lithium‐ion (Li‐ion) batteries, since sulfur electrode has high theoretical capacity (1672 mA h g_sul^?1) and this element is affordable. However, unlike their ubiquitous lithium ion (Li‐ion) counterparts, it is difficult to realize the commercialization of Li‐S battery. Because the shuttle effect of polysulfide inevitably results in the serious capacity degradation. Tremendous progress is devoted to approach this problem from the aspect of physical confinement and chemisorption of polysulfide. Owing to weak intermolecular interactions, physical confinement strategy, however is not effective when the battery is cycled long‐term. Chemisorption of polysulfide that derived from polar–polar interaction, Lewis acid–base interaction, and sulfur‐chain catenation, are proven to significantly suppress the shuttle effect of polysulfide. It is also discovered that the metal compounds have strong chemical interactions with polysulfide. Therefore, this review focuses on latest metal–organic frameworks metal sulfides, metal hydroxides, metal nitrides, metal carbides, and discusses how the chemical interactions couple with the unique properties of these metal compounds to tackle the problem of polysulfide shuttle effect.     

A gene for speed? The evolution and function of α‐actinin‐3

The alpha-actinins are an ancient family of actin-binding proteins that play structural and regulatory roles in cytoskeletal organisation and muscle contraction. alpha-actinin-3 is the most-highly specialised of the four mammalian alpha-actinins, with its expression restricted largely to fast glycolytic fibres in skeletal muscle. Intriguingly, a significant proportion ( approximately 18%) of the human population is totally deficient in alpha-actinin-3 due to homozygosity for a premature stop codon polymorphism (R577X) in the ACTN3 gene. Recent work in our laboratory has revealed a strong association between R577X genotype and performance in a variety of athletic endeavours. We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members. The alpha-actinin family provides a fascinating case study in molecular evolution, illustrating phenomena such as functional redundancy in duplicate genes, the evolution of protein function, and the action of natural selection during recent human evolution.     

Molecular‐Dynamics Simulation of Dioxygen Egress from 12/15‐Lipoxygenase?Arachidonic Acid Complex

Extensive random‐acceleration molecular‐dynamics (RAMD) simulations of the egress of dioxygen (O₂) from a model of rabbit 12/15‐lipoxygenase? arachidonic acid complex disclosed several exit portals in addition to those previously described from implicit ligand sampling calculations and limited MD simulations.     

Towards Squalamine Mimics: Synthesis and Antibacterial Activities of Head‐to‐Tail Dimeric Sterol?Polyamine Conjugates

Four dimeric sterol? polyamine conjugates have been synthesized from the homo‐ and hetero‐connection of monomeric sterol? polyamine analogs in a head‐to‐tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram‐positive bacteria, whereas their corresponding activities against Gram‐negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid‐containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid‐derived analogs. This is in contrast to the finding that a monomeric deoxycholic acid‐spermine conjugate was more active than the corresponding cholic acid‐derived analog.     

Correlation between sugar pucker and the orientation around the C3′?O3′ bond (Φ′) in 3′-mononucleotides

Classical potential functions (CPF) calculations on 3′-mononucleotides, the building blocks of nucleic acids, predict a correlation between the sugar ring pucker and the torsion angle Φ′ around the C3′? O3′ bond. In ribonucleotides, the value of Φ′ depends on the sugar pucker, viz. the C2′-endo sugar pucker is associated with Φ′ = 210° and 270°, while the C3′-endo sugar pucker favors only Φ′ = 210°. On the other hand, in deoxyribonucleotides, both sugar puckers show a preference for Φ′ = 180°. These theoretical predictions are fully corroborated by the results obtained from x-ray and nmr studies on mono-, di-, and polynucleotides.     

The involvement of rhamnolipids in microbial cell adhesion and biofilm development – an approach for control?

Biofilms are omnipresent in clinical and industrial settings and most of the times cause detrimental side effects. Finding efficient strategies to control surface‐growing communities of micro‐organisms remains a significant challenge. Rhamnolipids are extracellular secondary metabolites with surface‐active properties mainly produced by Pseudomonas aeruginosa. There is growing evidence for the implication of this biosurfactant in different stages of biofilm development of this bacterium. Furthermore, rhamnolipids display a significant potential as anti‐adhesive and disrupting agents against established biofilms formed by several bacterial and fungal species. Their low toxicity, biodegradability, efficiency and specificity, compared to synthetic surfactants typically used in biofilm control, might compensate for the economic hurdle still linked to their superior production costs and make them promising antifouling agents.