As a part of ongoing studies in developing new potent antimicrobial agents, a novel synthesis of 2-cyano-N-(1-(3-oxo-3H-benzofchromen-2-yl)ethylidene)acetohydrazide (3) has been reported. The latter ...compound was reacted with different reagents to give new heterocyclic compounds. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and mass spectral data. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.
Display omitted A variety of heterocyclic rings incorporating benzochromenone moiety were synthesized by reaction of 2-cyano-N-(1-(3-oxo-3H-benzofchromen-2-yl)ethylidene)acetohydrazide (3) with different reagents to give new compounds 4–18. The compounds 9 and 17 showed highest antibacterial inhibition.
•New heterocycles were synthesized incorporating oxygen, nitrogen and sulfur atoms.•Compounds were screened for their antimicrobial activity.•Some of the tested compounds exhibited promising activities.
Thirty compounds having 1-2-(5-substituted-2-benzoxazolinone-3-yl) acetyl-3,5-disubstitutedphenyl-2-pyrazoline structure and nine compounds having ...N′-(1,3-disubstitutedphenylallylidene)-2-(5-substituted-2-benzoxazolinone-3-yl)acetohydrazide skeleton were synthesized and evaluated as monoamine oxidase (MAO) inhibitors. All of the compounds exhibited selective MAO-A inhibitor activity in the nanomolar or low micromolar range. The results of the molecular docking for hydrazone derivatives supported the in vitro results. Five compounds, 6 (0.008 μM, Selectivity Index (SI): 9.70 × 10–4), 7 (0.009 μM, SI: 4.55 × 10–5), 14 (0.001 μM, SI: 8.00 × 10–4), 21 (0.009 μM, SI: 1.37 × 10–5), and 42 (0.010 μM, SI: 5.40 × 10–6), exhibiting the highest inhibition and selectivity toward hMAO-A and nontoxic to hepatocytes were assessed for antidepressant activity as acute and subchronic in mice. All of these five compounds showed significant antidepressant activity with subchronic administration consistent with the increase in the brain serotonin levels and the compounds crossed the blood–brain barrier according to parallel artificial membrane permeation assay. Compounds 14, 21, and 42 exhibited an ex vivo MAO-A profile, which is highly consistent with the in vitro data.
A series of hydrazide–hydrazones, based on a series of 4-substituted benzoic acid, were synthesized, and their structures were elucidated and screened for the antituberculosis activity against
...Mycobacterium tuberculosis H37Rv with the help of the BACTEC 460 radiometric system. Compound
3, 4-fluorobenzoic acid ((5-nitro)thiophen-2yl) methylenehydrazide showed the highest inhibitory activity in this series. The search of pharmacophores was done by means of the Electronic-Topological Method (ETM). The model developed in this study is supposed to be applied to the design, preparation and screening of new compounds of similar structure in order to further test and optimize the model with the eventual goal of preparing new anti-tubercular agents.
A series of hydrazide–hydrazones were synthesized, and their structures were elucidated and screened for the antituberculosis activity against
Mycobacterium tuberculosis H37Rv with the help of the BACTEC 460 radiometric system. The pharmacophores found formed a base for the antituberculosis activity prediction.
The synthesis and the anti-HIV-1 activity of novel benzo
disothiazole hydrazones are reported. Target compounds tested in MT-4 cells cultures for their anti-HIV properties against wild type HIV-1 and ...HIV strains carrying clinically relevant mutations (EFV
R, Y181C and K103/Y181C) showed good activity against wild type HIV-1 and against the EFV
R mutant. In terms of SAR the relevant result was that, in the class of benzisothiazole hydrazones, the benzo
disothiazol-3(2
H)-one moiety (compounds
1 and
4) is an essential structural requirement for the antiretroviral activity.
The synthesis and the anti-HIV-1 activity of novel benzo
disothiazole hydrazones are reported. The presence of the benzo
disothiazol-3(2
H)-one moiety (compounds
1 and
4) is an essential structural requirement for the antiretroviral activity.
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Phosphodiesterase 4 (PDE4) inhibitors have emerged as a new strategy to treat asthma and other lung inflammatory diseases. Searching for new PDE4 inhibitors, we previously reported the discover of ...LASSBio-448, a sulfonamide with potential to prevent and reverse pivotal pathological features of asthma. In this paper, two novel series of sulfonamide (6a-6m) and sulfonyl hydrazone (7a-7j) analogues of LASSBio-448 have been synthetized and evaluated for selective inhibitory activity toward cAMP-specific PDE4 isoforms. From these studies, we have identified 7j (LASSBio-1632) as a new anti-asthmatic lead-candidate associated with selective inhibition of PDE4A and PDE4D isoenzymes and blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue. In addition, it was able to relax guinea pig trachea on non-sensitized and sensitized animals and showed great TGI permeability.
Display omitted
•A new selective PDE4A and PDE4D inhibitor.•Good drug-like properties.•Blockade of airway hyper-reactivity (AHR) and TNF-α production in the lung tissue.•relaxant effects on guinea pig trachea.
A visible‐light photocatalytic generation of N‐centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to ...terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves deprotonation of an NH bond and photocatalytic oxidation to an N‐centered radical, thus obviating the need to prepare photolabile amine precursors or the stoichiometric use of oxidizing reagents.
Centered on N: A visible‐light‐induced photocatalytic generation of N‐centered hydrazonyl radicals has been accomplished for the first time. This approach allows efficient intramolecular addition of hydrazonyl radical to terminal alkenes, thus providing hydroamination and oxyamination products in good yields. Importantly, the protocol involves direct NH oxidation under mild reaction conditions. Ts=4‐toluenesulfonyl.
A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide
with various carbonyl compounds. Also, dehydrative-cyclocondensation of
...with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (M
) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds
,
, and
(-8.1 ± 0.33 kcal/mol, -8.0 ± 0.35 kcal/mol, and -8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (-6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.
Formaldehyde (FA), as a reactive carbonyl species, is endogenously generated in various biological processes. Abnormal levels of FA could lead to various cellular dysfunction and pathological ...conditions. Here, we develop a new activatable fluorescent probe for highly selective visualization of FA in living cells. Our probe (Naph-1) is designed using a naphthalene derivative as the fluorophore and hydrazone as a recognition site for FA. Naph-1 is essentially nonemissive. After reacting with FA, the amine moiety is converted into a Schiff base with electron-withdrawing ability and the fluorescence is simultaneously turned on due to synergetic intramolecular charge transfer and favoured excited state intramolecular proton transfer effects. Naph-1 exhibits a large Stokes shift upon reaction with FA. Furthermore, it possesses high selectivity and superior sensitivity toward FA with an estimated limit of detection of 0.35 μM. Moreover, Naph-1 is also successfully applied to image both endogenous and exogenous formaldehyde in living cells. These features demonstrate that Naph-1 holds great potential in the detection and imaging of formaldehyde in biological systems.
A new series of antioxidants, namely imines bearing the well-known free radical scavenger group 3,4,5-trimethoxybenzyloxy, was designed and synthesized. Theoretical calculations based on density ...functional theory (DFT) were performed to understand the antioxidant activities. Experimental studies evaluating the antioxidant activities of the compounds using DPPH and FRAP assays verified the predictions obtained by DMOL3 based on DFT.1. The DPPH radical scavenging activities depended on the substitution pattern of the aromatic aldehyde, with both the substitution type and position showing significant effects. Compounds 7b, 7c and 7d, which contain a phenolic hydroxyl group at the para position to the imine as well as, additional electron donating groups at the ortho-position to this hydroxyl group, exhibited IC50 values of 62, 75 and 106 μg/mL, respectively, and potent antioxidant activities against DPPH, which were better than that of the reference compound BHT. With the exception of compounds 7a and 7h with a phenolic hydroxyl group at the ortho position, all of the investigated compounds exhibited ferric reducing activities above 1000 μM. Correlation analysis between the two antioxidant assays revealed moderate positive correlation (r = 0.59), indicating differing antioxidant activities based on the reaction mechanism. Therefore, imines bearing a 3,4,5-trimethoxybenzyloxy group can be proposed as potential antioxidants for tackling oxidative stress.
A new series of antioxidants 7a–i, namely imines bearing the well-known free radical scavenger group 3,4,5-trimethoxybenzyloxy, was designed and synthesized. Theoretical calculations based on density functional theory (DFT) were performed to understand the antioxidant activities. Display omitted
•New hydrazones bearing a 3,4,5-trimethoxy benzyl moiety were synthesized.•Antioxidant activities were measured with DPPH and FRAP assays.•Antioxidant activities were rationalized based on theoretical studies.•A Pearson correlation analyses performed between the DPPH and FRAP activities.
Due to its important biological and pharmacological properties, in the field of medicinal chemistry and drug discovery, the N-acylhydrazone motif has shown to be extremely adaptable and promising. ...This scaffold has become a crucial component in the synthesis of numerous bioactive agents.
-Acylhydrazones are also interesting biological and synthetic tools due to their easy and straightforward synthesis. The current review provides a summary of the analgesic and anti-inflammatory activities of
-acylhydrazone derivatives over the past ten years. A brief discussion of structure-activity relationships is also provided which may guide researchers in medicinal chemistry to develop derivatives based on
-acylhydrazone scaffold as potent anti-inflammatory candidates.
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