The ordered π skeletons of covalent organic frameworks make them viable light‐emitting materials but their limited tunability has precluded further implementation. Here we report the synthesis of ...hydrazone‐linked frameworks which are stable in water, acid, and base, and demonstrate their utility as a platform for light emission. The polygonal backbone is designed to be luminescent and partially π conjugated while the pore wall is docked with single atom or unit to induce resonance, hyperconjugation, and tautomerization effects. These effects can be transmitted to the backbone, so that the framework can emit three primary colors of light. The wall can be perturbated with multiple surface sites, rendering the material able to edit diverse emission colors in a predesignable and digital way. The systems show high activity, stability, tunability, and sensibility: a set of features attractive for light‐emitting and sensing applications.
Topology‐directed polymerization enables the construction of highly emissive stable covalent organic frameworks linked by hydrazone bond. Perturbation of pore wall surface site can tune the emission to achieve three primary colors of light, rendering the materials able to edit various emission colors by organizing different surface sites onto the pore wall.
There has been considerable interest in the development of novel compounds with anticonvulsant, antidepressant, analgesic, antiinflammatory, antiplatelet, antimalarial, antimicrobial, ...antimycobacterial, antitumoral, vasodilator, antiviral and antischistosomiasis activities. Hydrazones possessing an azometine -NHN=CH- proton constitute an important class of compounds for new drug development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their biological activities. These observations have been guiding for the development of new hydrazones that possess varied biological activities.
Eighteen new N‐acylhydrazones (9a–r) containing the imidazo1,2‐apyridine scaffold were synthesized through a seven steps reaction sequence, ending with a condensation of ...2‐(3‐nitro‐H‐imidazo1,2‐apyridin‐2‐ylthio)acetohydrazide with various benzaldehyde derivatives (8a–r). All synthesized compounds were characterized by 1D NMR (1H and 13C NMR) and 2D NMR (NOESY) spectroscopic analyses and high‐resolution mass spectrometry (HRMS). The analysis of 1H NMR data performed at room temperature in deuterated dimethylsulfoxide (DMSO‐d6) revealed the presence of (E)‐2‐(3‐nitro‐H‐imidazo1,2‐apyridin‐2‐ylthio)‐N′‐benzylideneacetohydrazide (9a–r) as a mixture of two conformers, namely, syn‐periplanar E (sp E) and anti‐periplanar E (ap E). For all N‐acylhydrazones that were synthesized, the sp E conformer was found to be the major form except in the case of hydrazone derived from o‐hydroxybenzaldehyde.
The conformational analysis of N‐acylhydrazones was performed using NMR spectroscopy and describes the stereoelectronic interactions responsible for conformational stability.
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Naproxen is a common non-steroidal anti-inflammatory drug, which is the most usually used propionic acid derivative for the treatment of many types of diseases. In this study, a ...series of novel (S)-Naproxen derivatives bearing hydrazide-hydrazone moiety were designed, synthesized, and evaluated for anticancer activity. The structures of these compounds were characterized by spectral (1H–13C NMR, FT-IR, and HR-MS analyses) methods. All synthesized compounds were screened for anticancer activity against two different human breast cancer cell lines (MDA-MB-231 and MCF-7). Among them, (S)-2-(6-methoxynaphthalen-2-yl)-N'-{(E)-2-(trifluoromethoxy)phenylmethylidene} propanehydrazide (3a) showed the most potent anticancer activity against both cancer cell lines with a good selectivity (IC50 = 22.42 and 59.81 µM, respectively). Furthermore, the molecular modeling of these compounds was studied on Vascular Endothelial Growth Factor Receptor 2. Inhibition of VEGFR-2 and apoptotic protein Bcl-2 was investigated in MDA-MB-231 cells treated with compound 3a by using Western Blotting. Apoptosis was also detected by staining with DAPI in fluorescence microscopy. Flow Cytometry analyses related to cell cycle phases showed that a dramatic increase in S and M phases was established compared to untreated control cells indicating the cancer cell cycle arrest. The anticancer activity of compound 3a was investigated in the Ehrlich acid tumor model, a well-validated in vivo ectopic breast cancer model, in mice. Our results showed that compound 3a had anticancer activity and decreased the tumor volume in both low (60 mg/kg) and high (120 mg/kg) doses in mice.
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We describe the design, synthesis, and in vitro antimycobacterial activity of a series of novel simple hybrid hydrazides and hydrazide–hydrazones combining indole and pyridine nuclei. ...The compounds are derivatives of 1-acetylindoxyl or substituted indole-3-carboxaldehydes tethered via a hydrazine group by simple CN or double CN bonds with 3- and 4-pyridines, 1-oxide 3- and 4-pyridine carbohydrazides. The most active of 15 compounds showed MICs values against an INH-sensitive strain of Mycobacterium tuberculosis H37Rv equal to that of INH (0.05–2μg/mL). Five compounds demonstrated appreciable activity against the INH-resistant M. tuberculosis CN-40 clinical isolate (MICs: 2–5μg/mL), providing justification for further in vivo studies.
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search ...for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
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•A series of novel hydrazone derivatives bearing amide/urea moiety were synthesized.•All synthesized compounds were investigated for their MAO-A and MAO-B inhibitory ...activities.•Compounds 2a, 2k, 4a and 4i exhibited higher MAO-A inhibitory activity than moclobemide.•Interaction modes between the MAO-A enzyme and compound 4i were carried out with docking studies.
A novel series of hydrazone derivatives were designed and synthesized. Their structures were characterized by IR, 1H NMR, 13C NMR and HR-MS spectroscopic methods. The newly synthesized compounds were evaluated for their inhibitory activity against monoamine oxidase enzymes (MAO-A and MAO-B). Compounds 2a, 2k, 4a and 4i showed significant inhibitory activity against MAO-A, with IC50 value in the range of 0.084–0.207 µM compared to reference drug moclobemide (IC50 value = 6.061 µM). These compounds (2a, 2k, 4a and 4i) were exposed to cytotoxicity tests to establish their preliminary toxicological profiles and were found to be non-cytotoxic. Moreover, the most effective compound 4i was evaluated using enzyme kinetics and docking studies to elucidate the plausible mechanisms of inhibition of MAO-A. According to enzyme kinetic studies, compound 4i was a reversible and competitive inhibitor with similar inhibition features as the substrates. Also, it was seen that this compound was settled down very properly at the active site of MAO-A enzyme by doing important interactions owing to the docking studies. Finally, ADME predictions were applied to estimate pharmacokinetic profiles of synthesized compounds. According to calculated ADME predictions, all parameters of the compounds were within the standard ranges in terms of “Rule of Five” and “Rule of Three” and it was detected that the synthesized compounds (2a-4i) have good and promising pharmacokinetic profiles.
Watching C 'n' N: Hydrazones and oximes are common conjugates but are labile to hydrolysis. The hydrolytic stabilities of isostructural hydrazones and one oxime were determined at pD 5.0–9.0. The ...rate constant for the acid‐catalyzed hydrolysis of the oxime was nearly 103‐fold lower than those for simple hydrazones, and a trialkylhydrazonium ion (formed after condensation) was even more stable than the oxime.
Objectives
The in vitro antileishmanial effect of analogues of resveratrol (AR) present in the N‐aryl imines and N‐aryl hydrazones series was investigated. In addition, possible parasite targets were ...evaluated.
Methods
Antipromastigote activity of Leishmania amazonensis, L. braziliensis and L. infantum, as well as the cytotoxicity on macrophages was determined by MTT assay and L. braziliensis‐infected macrophages effect by Giemsa stain. After staining, effects on the parasite targets were analysed by flow cytometry or by fluorescence microscopy.
Key‐findings
Among the tested compounds, the derivative AR26 showed the best effect against promastigotes of all Leishmania species (IC50 < 3.0 µg/ml), being more active than miltefosine, the control drug. AR26 was also effective against amastigotes of L. braziliensis (IC50 = 15.9 µg/ml), with low toxicity to mammalian cells. The evaluation of mechanism of action of AR26 on L. braziliensis promastigotes indicates mitochondrial potential depolarization, plasma membrane permeabilization, interference in the progression of the cell cycle and accumulation of autophagic vacuoles. In addition, any increase of the reactive oxygen species levels was detected in the treated L. braziliensis‐macrophages.
Conclusions
Data indicate that the antileishmanial activity of AR26 is related to multitarget action, and the resveratrol analogues could be used in future studies as antileishmanial agent.
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