Acylhydrazone Derivatives Research Articles

Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Acylhydrazone Derivatives Containing Carbazole Moity

Synthesis and Cdc25B/PTP1B Inhibitory Activity Evaluation of Novel Acylhydrazone Derivatives Containing Carbazole Moity

Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives.

The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives: N'-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-123) and N'-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-99). An air pouch induced by carrageenan was used for screening the best dose of R-99 and R-123. Using this mouse model, leukocyte migration and cytokine levels (TNF-α and IL-1β) were determined. Paw edema induced by several phlogistic agents and vascular permeability induced by acetic acid were employed to investigate the mechanism of action of the isoxazoline-acylhydrazone derivatives. A docking study was performed with the human histamine H1 receptor to investigate potential antihistaminic activity. Treatment with the compounds reduced leukocyte migration in the air pouch at all doses tested. TNF-α and IL-1β levels were similarly reduced by the two compounds. Vasoactive amines were inhibited in models of paw edema induced by several agents and vascular permeability induced by acetic acid. The docking study suggests that R-99 and R-123 may be inhibitors of the histamine H1 receptor. In conclusion, the results indicate that R-99 and R-123 exhibit promising anti-inflammatory activity related to their ability to inhibit TNF-α, IL-1β, and vasoactive amine production, as well as reduce leukocyte migration and inhibit mast cell degranulation.

Spectrochemical and theoretical approaches for acylhydrazone-based fluoride sensors

Acylhydrazone derivatives N′-[1-(2-fluorophenyl)ethylidene]pyridine-3-carbohydrazide (R1) and N′-[2-fluorobenzylidene]benzohydrazide (R2) were synthesized from their corresponding hydrazides and characterized by spectroscopic methods. The response of these acylhydrazones towards different anions was studied by colorimetric and spectrofluorometric methods in acetonitrile. The receptors exhibited a specific response towards fluoride ion. The binding affinity of the receptors with fluoride anion was studied by fluorescence spectroscopic techniques and ab initio density functional theory calculations with Becker’s three-parameter Lee–Yang–Par (B3LYP) exchange functional with 6-311G basis set.

Synthesis and Antibacterial Activity of C-7 Acylhydrazone Derivatives of Dehydroabietic Acid

Seven new C-7 acylhydrazone derivatives of dehydroabietic acid were synthesised from dehydroabietic acid through benzylic oxidation, condensation with hydrazine hydrate, followed by nucleophilic substitution reactions with a variety of substituted aromatic acids. The structures of the synthesised compounds were characterised by IR, 1H NMR and MS. The antibacterial activities of the synthesised compounds were evaluated by the disk diffusion method. Antibacterial activity studies showed that C-7 acylhydrazone derivatives of dehydroabietic acid exhibited inhibitory activities against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. Among the seven compounds, dehydroabietic acid p-fluorobenzoyl hydrazone showed the strongest inhibitory activity against B. subtilis and S. aureus.

Luminescent columnar liquid crystals based on AIE tetraphenylethylene with hydrazone groups bearing multiple alkyl chains

A series of novel tetraphenylethylene aromatic acylhydrazone derivatives 11, 12 and 13 with 4, 8 or 12 alkyl chains were designed and synthesized in yields of 82–85%. Studies on the mesomorphic properties suggested the ordered hexagonal columnar mesophase for compounds 11, 12 and 13. The increase in the number of alkyl chains was favourable for decreasing the phase-transition temperatures and extending the mesophase temperature range. Further, samples 11, 12 and 13 presented an excellent AIE effect. The fluorescence intensities increased by 70, 84 and 43 times for samples 11, 12 and 13, respectively. The absolute fluorescence quantum yields were 18.7%, 27.4% and 23.8% in solid films at room temperature and 6.7%, 24.2% and 17.3% in the mesophase. These results suggested that the number of alkyl chains greatly influenced the fluorescence emission and sample 12 with 8 alkyl chains exhibited the strongest fluorescence emission. Sample 12 also displayed the electroluminescence performance on OLED device.

Mechanofluorochromic behavior of anthracene-based acylhydrazone derivatives

Two anthracene-based derivatives, having one or two acylhydrazone branches attached on the anthracene, namely, asymmetrical AHP-1 and symmetrical AHBP-1 were designed. These compounds exhibited mechanofluorochromic behavior with the emission colors reversibly changing upon grinding and recrystallizing. The mechanofluorochromic mechanism was explored and ascribed to the crystalline-amorphous phase transformation. In addition, the red-shifted extent of fluorescent emission of the ground AHBP-1 samples was more than that of AHP-1.

Synthesis and Antimicrobial Activities of Novel Quinazolinone Acylhydrazone Derivatives Containing the Indole Moiety

A series of novel quinazolinone acylhydrazone derivatives containing the indole moiety were designed, synthesized, and evaluated for their inhibition activities against some important phytopathogens in vitro. Antibacterial experiments indicated that some compounds exhibited remarkable inhibition activities against tested bacteria. Especially, the EC50 values of 7a (EC50 = 55.13 μg/mL against Xoo, EC50 = 56.92 μg/mL against Rs) demonstrated the best antibacterial activities against Xoo and Rs than the other compounds, and the control agents Bismerthiazol (EC50 = 89.80 μg/mL against Xoo) and Thiodiazole copper (EC50 = 189.52 μg/mL against Rs), moreover, compound 7o (EC50 = 50.80 μg/mL) displayed the excellent activity against Xac than the control Bismerthiazol (EC50 = 56.92 μg/mL).

Theoretical and experimental characterization of 1,4-N⋯S σ-hole intramolecular interactions in bioactive N-acylhydrazone derivatives

Sigma-hole (σ-hole) bonds are interactions that are gaining special attention in medicinal chemistry.

Synthesis and Antibacterial Activity of 2-Morpholino-1-propyl-1H-indole-3-substituted Acylhydrazone Derivatives

Synthesis and Antibacterial Activity of 2-Morpholino-1-propyl-1<i>H</i>-indole-3-substituted Acylhydrazone Derivatives

Hydrazone Derivatives Enhance Antileishmanial Activity of Thiochroman-4-ones.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC50 values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS).

Crystal structures of three ortho-substituted N-acyl-hydrazone derivatives.

To explore the effect of the nature of substitutions on the structural parameters and hydrogen-bond inter-actions in N-acyl-hydrazone derivatives, the crystal structures of three ortho-substituted N-acyl-hydrazone derivatives, namely (E)-N-{2-[2-(2-chloro-benzyl-idene)hydrazin-yl]-2-oxoeth-yl}-4-methyl-benzene-sulfon-amide, C16H16ClN3O3S (I), (E)-N-{2-[2-(2-methyl-benzyl-idene)hydrazin-yl]-2-oxoeth-yl}-4-methyl-benzene-sulfonamide, C17H19N3O3S (II), and (E)-N-{2-[2-(2-nitro-benzyl-idene)hydrazin-yl]-2-oxoeth-yl}-4-methyl-benzene-sulfonamide, C16H16N4O5S (III), have been determined. The structures of the three compounds display similar mol-ecular conformations and hydrogen-bond patterns. The hydrazone part of the mol-ecule, C-C-N-N=C, is almost planar in all the compounds, with the C-C-N-N and C-N-N=C torsion angles being 179.5 (3) and 177.1 (3)°, respectively, in (I), -179.4 (2) and -177.1 (3)° in (II) and -179.7 (2) and 173.4 (2)° in (III). The two phenyl rings on either side of the chain are approximately parallel to each other. In the crystal, the mol-ecules are linked to each other via N-H⋯O hydrogen bonds, forming ribbons with R22(8) and R22(10) ring motifs. The introduction of electron-withdrawing groups (by a chloro or nitro group) to produce compounds (I) or (III) results in C-H⋯O hydrogen-bonding inter-actions involving the sulfonyl O atoms of adjacent ribbons, forming layers parallel to the ab plane in (I) or a three-dimensional network in (III). In (III), one O atom of the nitro group is disordered over two orientations with refined occupancy ratio of 0.836 (12):0.164 (12).

Synthesis and biological assessment of novel acylhydrazone derivatives of 2-methyl-1,4-naphthoquinone

Synthesis and biological assessment of novel acylhydrazone derivatives of 2-methyl-1,4-naphthoquinone

Microwave-assisted synthesis, characterization and bioassay of acylhydrazone derivatives as influenza neuraminidase inhibitors

A series of acylhydrazone derivatives (4a–4s) were synthesized via microwave irradiation with short reaction time and good yields. The crystal structure of compound 4j was further determined by single-crystal X-ray diffraction. All of the derivatives were evaluated in vitro for influenza neuraminidase inhibitory activities. Among them, compounds 4l and 4n showed the most potent activity with IC50 values of 59.86 and 49.97 μM, respectively. Molecular docking was performed to study the interactions between the protein and compound 4n. The docking result revealed the potential dual-site binding model of the title compounds (“430 cavity-Linker-SA cavity” model) which provided a new idea for the design of novel influenza neuraminidase inhibitors.

Mechano- and thermo-responsive fluorescent xerogel based on anthracene-substituted acylhydrazone derivatives

This report describes that the luminescence of anthracene-based acylhydrazone derivative AHP−mB8 can be tuned by physical stimuli, such as heating and grinding. The AHP−mB8 xerogel from cyclohexane shows obviously mechanofluorochromic behaviour with the emission colors changing from blue to green upon grinding, whereas the ethanol xerogel shows yellowish-green light emission, which is almost unchanged after grinding. In the other hand, the ethanol xerogel exhibits thermofluorochromic with the emission colors changing from yellowish-green to blue upon heating. Based on SEM, XRD, DSC and Uv-vis studies, the observed mechanofluorochromism and thermochromism of AHP−mB8 is attributed to the result of solid–solid phase transition.

Corrigendum to: Novel Thymohydroquinone Derivatives as Potential Anticancer Agents: Design, Synthesis, and Biological Screening

The safety and efficacy of naturally occurring anticancer agents and their derivatives such as thymoquinone (TQ) and thymohydroquinone (THQ) have gained a rapidly growing interest. In an attempt to develop novel anticancer agents with superior activity, TQ was allowed to react with hydrazine hydrate, producing hydrazino thymohydroquinone 3. This new intermediate was subsequently reacted with various isocyanates, isothiocyanates, and acyl halides, affording three series of semicarbazone, semithiocarbazone, and acyl hydrazone derivatives, respectively. Subsequently, the anticancer activity of all the newly synthesised compounds against a panel of cancer cell lines was evaluated. Initial screening of the ability of the test compounds to inhibit cancer cell viability using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that compounds 5d and 6 exerted better activity against breast cancer than TQ, with half-maximal inhibitory concentration (IC50) values of 9.6 and 10.0?M, respectively. MTT results were confirmed by the ability of these compounds to elicit apoptotic cell death through the activation of caspase 3/7 enzymes. Together, the present work provided a novel class of THQ-based derivatives with potent anticancer and apoptosis properties, thereby warranting further optimisation of these derivatives as novel members in cancer treatment protocols.

E-Z isomerization of the -C[double bond, length as m-dash]N- bond in anthracene-based acylhydrazone derivatives under visible light.

The photoresponsive behaviour of AHP-mB8 upon irradiation by visible light was demonstrated to be due to the E-Z isomerizations of the -C[double bond, length as m-dash]N- group, rather than the photodimerization of anthracene groups. In addition, the Z-isomer of AHP-mB8 was stable at room temperature. AHP-mB8 organogels showed visible light induced gel-sol transition and its mechanism was proposed.

Synthesis of a New Polyfunctionalised Pyrimidine-4-carboxylate and Its Application for the Construction of a Series of Pyrimidine Derivatives

The synthesis of a new and versatile polyfunctionalised pyrimidine-4-carboxylate, along with the study of its reactivity against 1,2-dinucleophiles and 1,4-dinucleophiles, is reported. These simple and efficient methodologies allowed for the synthesis of novel pyrimidine derivatives such as pyrimido[4,5- d ]pyridazin-8-one-5-carboxylates and their corresponding carbohydrazides and N -acylhydrazone (NAH) derivatives, pyrimido[4,5- d ][1,2]oxazin-8-one and its corresponding carbohydrazide derivative, and 3-pyrimidinylquinoxaline-2-one and its corresponding carbohydrazide. Furthermore, pyrimidine hydroxyimino derivatives were also prepared.

Design, synthesis and evaluation of antitumor activity of new rotundic acid acylhydrazone derivatives.

In light of the important antitumor activity of acylhydrazone compounds and based on our previous study, 18 new rotundic acid (RA) acylhydrazone derivatives were synthesized. All of the compounds were characterized by their spectroscopic data. The antiproliferative activity of the compounds was evaluated in vitro via the MTT method in three tumor cell lines, including A-375 (human malignant melanoma cells), SPC-A1 (human lung adenocarcinoma) and NCI-H446 (small cell lung cancer). The results showed that the antiproliferative activity of all of the compounds on the NCI-H446 cell line did not increase compared to RA, however, most of the derivatives exhibited higher activity against the A375 and SPC-A1 cell lines as compared to RA. Importantly, the antiproliferative activities of compounds 5a and 5b were the highest among the compounds, with IC(50) values <10 μM. Collectively, compounds 5a and 5b may act as potential anti-tumor agents in the future.

Synthesis, Characterization, and Conformational Study of Acylhydrazones of α,β‐Unsaturated Aldehydes

ABSTRACTNew acylhydrazone derivatives 1–6 have been synthesized by condensation of tert‐butylphenoxyhydrazide and cinnamaldehyde A or β‐chloro‐α,β‐unsaturated aldehydes B–F. They were characterized by IR, (1H, 13C, 19F) nuclear magnetic resonance (NMR), and high‐resolution mass spectroscopy. The NMR data show the existence of the cis/trans‐amide conformers due to N–C(O) bond rotation in addition to the E/Z isomers around the C=C bond of some of the starting aldehydes. The solvent polarity effects on the ratios of the cis/trans‐amide rotamers have also been investigated. Importantly, rotational barriers around the N–C(O) bond for all compounds 1–6 (62.9–68.8 kJ mol–1) were calculated using the coalescence‐temperature method according to the Eyring equation. The results are discussed and compared with those previously reported for related acylhydrazones of aryl adehydes and acetone.

Novel Thymohydroquinone Derivatives as Potential Anticancer Agents: Design, Synthesis, and Biological Screening

The safety and efficacy of naturally occurring anticancer agents and their derivatives such as thymoquinone (TQ) and thymohydroquinone (THQ) have gained a rapidly growing interest. In an attempt to develop novel anticancer agents with superior activity, TQ was allowed to react with hydrazine hydrate, producing hydrazino thymohydroquinone 3. This new intermediate was subsequently reacted with various isocyanates, isothiocyanates, and acyl halides, affording three series of semicarbazone, semithiocarbazone, and acyl hydrazone derivatives, respectively. Subsequently, the anticancer activity of all the newly synthesised compounds against a panel of cancer cell lines was evaluated. Initial screening of the ability of the test compounds to inhibit cancer cell viability using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that compounds 5d and 6 exerted better activity against breast cancer than TQ, with half-maximal inhibitory concentration (IC50) values of 9.6 and 10.0 μM, respectively. MTT results were confirmed by the ability of these compounds to elicit apoptotic cell death through the activation of caspase 3/7 enzymes. Together, the present work provided a novel class of THQ-based derivatives with potent anticancer and apoptosis properties, thereby warranting further optimisation of these derivatives as novel members in cancer treatment protocols.