Search Results (8)

Herein we describe the development of the first model amphiphilic polymer conetwork (APCN) comprising a short hydrophobic hexa(L-alanine) segment being the outer block of an amphiphilic four-armed star block copolymer with inner poly(ethylene glycol) (PEG) blocks bearing benzaldehyde terminal groups and end-linked with another four-armed star PEG homopolymer (tetraPEG star) bearing aryl-substituted acylhydrazide terminal groups. The present successful synthesis that yielded the peptide-containing model APCN was preceded by several unsuccessful efforts that followed different synthetic strategies. In addition to the synthetic work, we also present the structural characterization of the peptide-bearing APCN in D₂O using small-angle neutron scattering (SANS). Full article

The framework of 1,3,4-oxadiazine is crucial for numerous bioactive molecules, but only a limited number of synthetic methods have been reported for its production. In 2015, Wang’s group developed a 4-(dimethylamino)pyridine (DMAP)-catalyzed [2 + 4] cycloaddition of allenoates with N-acyldiazenes, which provided an atom-efficient route for 1,3,4-oxadiazines. However, the practicality of this method was limited by the instability of N-acyldiazenes as starting materials. Building upon our ongoing research about the aerobic oxidation of hydrazides and their synthetic applications, we hypothesized that aerobic oxidative cycloadditions using acylhydrazides instead of N-acyldiazenes may provide a more practical synthetic route for 1,3,4-oxadiazines. In this manuscript, we describe a one-pot synthetic protocol for 1,3,4-oxadiazines from acylhydrazides and allenoates. The developed one-pot protocol consists of aerobic oxidations of acylhydrazides into N-acyldiazenes using NaNO₂ and HNO₃, followed by the DMAP-catalyzed cycloaddition of allenoate with the generated N-acyldiazenes. A variety of 1,3,4-oxadiazines were produced in good to high yields. In addition, the practicality of the developed method was demonstrated by a gram-scale synthesis of 1,3,4-oxadiazine. Full article

Many Gram-negative pathogenic bacteria rely on a functional type III secretion system (T3SS), which injects multiple effector proteins into eukaryotic host cells, for their pathogenicity. Genetic studies conducted in different host-microbe pathosystems often revealed a sophisticated regulatory mechanism of their T3SSs, suggesting that the expression of T3SS is tightly controlled and constantly monitored by bacteria in response to the ever-changing host environment. Therefore, it is critical to understand the regulation of T3SS in pathogenic bacteria for successful disease management. This review focuses on a model plant pathogen, Dickeyadadantii, and summarizes the current knowledge of its T3SS regulation. We highlight the roles of several T3SS regulators that were recently discovered, including the transcriptional regulators: FlhDC, RpoS, and SlyA; the post-transcriptional regulators: PNPase, Hfq with its dependent sRNA ArcZ, and the RsmA/B system; and the bacterial second messenger cyclic-di-GMP (c-di-GMP). Homologs of these regulatory components have also been characterized in almost all major bacterial plant pathogens like Erwiniaamylovora, Pseudomonassyringae, Pectobacterium spp., Xanthomonas spp., and Ralstonia spp. The second half of this review shifts focus to an in-depth discussion of the innovation and development of T3SS inhibitors, small molecules that inhibit T3SSs, in the field of plant pathology. This includes T3SS inhibitors that are derived from plant phenolic compounds, plant coumarins, and salicylidene acylhydrazides. We also discuss their modes of action in bacteria and application for controlling plant diseases. Full article

In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N′-acylhydrazide motifs combined with the 3,5-bis(trifluoromethyl)phenyl moiety. Eleven novel compounds were synthesized and subject to biological evaluation. The analyzed compounds exhibit a diversified range of affinities for the µ opioid receptor (MOR), rather low δ opioid receptor (DOR) affinities, and no appreciable neurokinin-1 receptor binding. In three out of four pairs, N-acylhydrazone-based derivatives bind MOR better than their N’-acylhydrazide counterparts. The best of the novel derivatives have similar low nanomolar MOR binding affinity as the reference opioids, such as morphine and biphalin. The obtained order of MOR affinities was compared to the results of molecular docking. In vivo, four tested compounds turned out to be relatively strong analgesics. Finally, the NAH-based analogues reduce the number of melanoma cells in cell culture, while their N′-acylhydrazide counterparts do not. The antimelanoma properties are roughly correlated to the lipophilicity of the compounds. Full article

Self-healing hydrogels have drawngreat attention in the past decade since the self-healing property is one of the characteristics of living creatures. In this study, poly(acrylamide-stat-diacetone acrylamide) P(AM-stat-DAA) with a pendant ketone group was synthesized from easy accessible monomers, and thermo-responsive self-healing hydrogels were prepared through a series of diacylhydrazide compounds cross-linking without any additional stimulus. Although the copolymers do not show thermo-response, the hydrogels became thermo-responsive andboth the lower critical solution temperature (LCST) and upper critical solution temperature (UCST) varied with the composition of the copolymer and structure of cross-linkers. With a dynamic covalent bond connection, the hydrogel showed gel-sol-gel transition triggered by acidity, redox, and ketone to acylhydrazide group ratios. This is another interesting cross-linking induced thermo-responsive (CIT) hydrogel with different properties compared to PNIPAM-based thermo-responsive hydrogels. The self-healing hydrogel with CIT properties could have great potential for application in areas related to bioscience, life simulation, and temperature switching. Full article

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of dehydroabietic acid (DHA) derivatives bearing an acylhydrazone moiety were designed and synthesized by the condensation between dehydroabietic acylhydrazide (3) and a variety of substituted arylaldehydes. The inhibitory activities of these compounds against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), and BEL-7402 (liver) human carcinoma cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay in vitro. The screening results revealed that many of the compounds showed moderate to high levels of anticancer activities against the tested cancer cell lines and some displayed similar potent inhibitory activities to the commercial anticancer drug cisplatin, while they exhibited lower cytotoxicity against normal human liver cell (HL-7702). Particularly, compound 4w, N’-(3,5-difluorobenzylidene)-2-(dehydroabietyloxy)acetohydrazide, with an IC₅₀ (50% inhibitory concentration) value of 2.21 μM against HeLa cell, was about 17-fold more active than that of the parent compound, and showed remarkable cytotoxicity with an IC₅₀ value of 14.46 μM against BEL-7402 cell. These results provide an encouraging framework that could lead to the development of potent novel anticancer agents. Full article

A focused library of [4-(2-hydroxyphenyl)thiazol-2-yl]methanones was prepared in a four-step synthesis with the aim to obtain potent inhibitors of type III secretion in Gram-negative bacteria. The compounds are potential bioisosteres of salicylidene acylhydrazides that are a known class of type III secretion inhibitors. Full article

Salicylidene acylhydrazides are inhibitors of type III secretion in several Gram-negative pathogens. To further develop the salicylidene acylhydrazides, scaffold hopping was applied to replace the core fragment of the compounds. The novel 2-(2-amino-pyrimidine)-2,2-difluoroethanol scaffold was identified as a possible analog to the salicylidene acylhydrazide core structure. The synthesis of a library of 2-(2-amino-pyrimidine)-2,2-difluoro-ethanols is described in this paper. Full article