Acylhydrazone Derivatives Research Articles

Synthesis, Spectroscopic Characterization, DFT, Molecular Docking, Catechol Oxidase Activity, and Anti-SARS-CoV-2 of Acylhydrazone Derivatives

In the present work, five pyrazole-hydrazone biomolecule ligands (L1–L5) were synthesized by condensation between 1H-pyrazole-3-carbohydrazide (2) and aromatic benzaldehydes. Their corresponding structures were elucidated employing NMR and FT-IR spectra and ESI-MS data. Li-Cu(II) complexes (i = 1–5) were evaluated for catecholase activity in situ at standard conditions. The findings disclose that the catecholase oxidation rate varies with the substituted functional groups in ligand and the anion type in the copper (II) salt. Catecholase activity results showed that the L(i = 1–5) -Cu(II)SO4 complexes exhibited efficient catalytic activity, and a maximum activity of 105 ± 42 µM.min−1 is obtained with L5-Cu(II)SO4. DFT and NBO calculations have been carried out to identify the global reactivity and the strength of interaction bonds between the donors and acceptors in L1–L5. The optimized structure of L1–L3 and L5 were found planar, while that of L4 is out of the molecular plan and forms a torsion angle of 18 degrees due to the presence of methoxy and hydroxyl group at meta and para. In L4, the 5-methyl-1H-pyrazole moiety. NBO findings show that the strongest interactions in L1–L5 are those involved in the electronic transition from π-bonding → π*-antibonding and LP → π*- antibonding molecular orbitals. Further, the anti-SARS-CoV-2 of L1–L5 are investigated by estimating their binding affinities into its binding. The docking results reveal that L1–L5 may act as SARS-CoV-2 main protease inhibitors with estimated binding energies in the −6.00 to −8.0 kcal.mol−1 range.

Design, Synthesis, and Antiviral and Fungicidal Activities of 4-Oxo-4H-quinolin-1-yl Acylhydrazone Derivatives.

To discover novel antiviral agents, based on the high antiviral activity of (4-oxo-4H-quinolin-1-yl)-acetic acid hydrazide (C), a series of 4-oxo-4H-quinoline acylhydrazone derivatives were designed, synthesized, and first evaluated for their antiviral and fungicidal activities. Most acylhydrazone derivatives exhibited moderate to good antiviral activities in vivo. The inactive, curative, and protective activities of compounds 4 (51.2, 47.6, and 46.3%), 11 (49.6, 43.0, and 45.2% at 500 mg/L), and 17 (47.1, 49.2, and 44.1%) were higher than those of ribavirin (39.2, 38.0, and 40.8%) at 500 mg/L. Molecular docking showed that compound 4 exhibited a stronger affinity to TMV coat protein (TMV-CP) than ribavirin, with a binding energy (-6.89 kcal/mol) slightly lower than that of ribavirin (-6.08 kcal/mol). Microscale thermophoresis showed that compound 4 (K d = 0.142 ± 0.060 μM) exhibited a strong binding ability to TMV-CP, superior to that of ribavirin (K d = 0.512 ± 0.257 μM). The results of transmission electron microscopy showed that compound 4 hindered the self-assembly and growth of TMV. The antifungal activities of most compounds were moderate at 50 mg/L, among which compounds 12 and 21 exhibited a 72.1 and 76.5% inhibitory rate against Physalospora piricola, respectively. Meanwhile, compound 16 exhibited a 60% inhibitory rate against Cercospora arachidicola Hori at 50 mg/L.

Acyl hydrazone derivatives with trifluoromethylpyridine as potential agrochemical for controlling plant diseases.

Crops are consistently under siege by a multitude of pathogens. These pathogenic microorganisms, including viruses and bacteria, result in substantial reductions in quality and yield globally by inducing detrimental crop diseases, thus posing a significant challenge to global food security. However, the biological activity sepectrumof commercially available pesticides is limitedand the pesticide efficacy is poor, necessitating the urgent development of broad-spectrum and efficient strategies for crop disease prevention and control. The bioassay results revealed that certain target compounds demonstrated outstanding in vivo antiviral efficacy against cucumber mosaic virus and tobacco mosaic virus. In particular, compound D6 showed remarkable antiviral activity against CMV, significantly higher than that of the control agent ningnanmycin. Mechanism of action studies have shown that compound D6 could enhance the activity of defense enzymes and upregulate the expression of genes related to disease resistance, thereby enhancing the antiviral effects in plants. In addition, these compounds displayed superior inhibitory activity against plant bacterial diseases. For Xoo, compound D10 showed an excellent inhibitory effect that was better than that of the control agent bismerthiazol. Scanning electron microscopy and fluorescence double-staining experiments revealed that compound D10 effectively inhibited bacterial growth by disrupting the cell membrane. A series of trifluoromethyl hydrazone derivatives were designed and synthesized, and it was found that they have control effects on plant viruses and bacterial diseases. In addition, this study revealed the mechanism of action of the active compounds and demonstrated their potential as multifunctional crop protectants. © 2024 Society of Chemical Industry.

A biologically inspired fluorescent probe with enhanced sensing performance for detection of Al3+ based on metal replacement strategy

Salicylaldehyde acyl-hydrazone derivatives have been widely applied to design fluorescent probe for Al3+ detection, but they are always restricted to detect Al3+ in water and actual samples by their poor solubility, low sensitivity, and long response time. Biologically inspired, four salicylaldehyde acyl-hydrazone compounds were designed and synthesized and H4L1 as one of them was selected for in-situ assembly of the ytterbium complex (FP-Al), which has been developed to be a new fluorescent probe for Al3+ detection by the central mental displacement process. The in-situ structure transformation from FP-Al to Al-L was fully characterized by X-ray crystal structure analysis, 1H NMR, FT-IR, and spectral analysis. The intrinsic driving force was explained and elaborated by theoretical calculation. FP-Al showed a significant visible fluorescence enhancement and near-infrared luminescence decreased upon the addition of Al3+. Compared with the ligand H4L1, FP-Al showed enhanced sensing performance during Al3+ detection, especially in improving water solubility and selectivity to Al3+, promoting response speed, reducing background fluorescence and increase cell-membrane permeability. The application of spontaneous metal replacement reaction might be able to provide a new strategy to develop high-performance optical chemo-sensors.

Photo/Mechanical/Acidic Multi-Stimuli Responses and Information Encryption Design of Acylhydrazone Derivative.

Stimuli-responsive crystalline materials have received much attention for being potential candidates of smart materials. However, the occurrence of polymorphism-driven stimuli responses in crystalline materials remains interesting but rare. Herein, three polymorphs of an acylhydrazone derivative, N'-[(E)-(1-benzofuran-2-yl) methylidene] pyridine -4-carbohydrazide (BFMP) were prepared. Form-1 undergoes a photomechanical response via E→Z photoisomerization under UV irradiation, accompanied by a decrease in fluorescence intensity and a change from colorless to yellow. Two types of Z→E thermal isomerization mechanisms with significant differences in conversion rate were observed at different temperatures in form-1. The solid-melt-solid transition has a faster conversion rate compared to the solid-solid transition due to freedom from lattice confinement. The transition from form-2 to form-3 can be achieved under grinding, coupled with a significant decrease in fluorescence intensity. The similar molecular stacking pattern of form-2 and form-3 provides a structural basis for the grinding-induced crystalline transition behavior. In addition, the presence of the pyridine moiety imparts an acidochromic property. The combination of photochromism and acidochromism explores the possible applications of acylhydrazone derivatives in information encryption.

Continuous, Solvent-Free, and Mechanochemical Synthesis of N-Acylhydrazone Derivatives by Spiral Gas–Solid Two-Phase Flow

Continuous, Solvent-Free, and Mechanochemical Synthesis of <i>N</i>-Acylhydrazone Derivatives by Spiral Gas–Solid Two-Phase Flow

Isatin-tethered halogen-containing acylhydrazone derivatives as monoamine oxidase inhibitor with neuroprotective effect

Sixteen isatin-based hydrazone derivatives (IS1–IS16) were synthesized and assessed for their ability to inhibit monoamine oxidases (MAOs). All the molecules showed improved inhibitory MAO-B activity compared to MAO-A. Compound IS7 most potently inhibited MAO-B with an IC50 value of 0.082 μM, followed by IS13 and IS6 (IC50 = 0.104 and 0.124 μM, respectively). Compound IS15 most potently inhibited MAO-A with an IC50 value of 1.852 μM, followed by IS3 (IC50 = 2.385 μM). Compound IS6 had the highest selectivity index (SI) value of 263.80, followed by IS7 and IS13 (233.85 and 212.57, respectively). In the kinetic study, the Ki values of IS6, IS7, and IS13 for MAO-B were 0.068 ± 0.022, 0.044 ± 0.002, and 0.061 ± 0.001 μM, respectively, and that of IS15 for MAO-A was 1.004 ± 0.171 μM, and the compounds were reversible-type inhibitors. The lead compounds were central nervous system (CNS) permeable, as per parallel artificial membrane permeability assay (PAMPA) test results. The lead compounds were examined for their cytotoxicity and potential neuroprotective benefits in hazardous lipopolysaccharide (LPS)-exposed SH-SY5Y neuroblastoma cells. Pre-treatment with lead compounds enhanced anti-oxidant levels (SOD, CAT, GSH, and GPx) and decreased ROS and pro-inflammatory cytokine (IL-6, TNF-alpha, and NF-kB) production in LPS-intoxicated SH-SY5Y cells. To confirm the promising effects of the compound, molecular docking, dynamics, and MM-GBSA binding energy were used to examine the molecular basis of the IS7-MAO-B interaction. Our findings indicate that lead compounds are potential therapeutic agents to treat neurological illnesses, such as Parkinson's disease.

Design, synthesis and insecticidal activity of novel Isoxazoline Acylhydrazone compounds.

Nowadays, the diamondback moth has ascended to become one of the most formidable pests plaguing cruciferous vegetables. Consequently, the exigency for the development of efficacious pesticide candidates for crop protection has never been more paramount. In response to this pressing need, this study presents a compendium of novel isoxazoline derivatives, incorporating acylhydrazone moieties, synthesized with the express purpose of serving as potential insecticides. The structures of these derivatives were confirmed using Proton nuclear magnetic resonance (1 H NMR), Carbon-13 nuclear magnetic resonance (13 C NMR), and high-resolution mass spectrometry (HR-MS). Most of these derivatives demonstrated effective insecticidal activities against Plutella xylostella. Notably, compound E3 exhibited exceptional insecticidal activity against Plutella xylostella (LC50 = 0.19 mg L-1 ), surpassing the effectiveness of ethiprole (LC50 = 3.28 mg L-1 ), and comparable to that of fluxametamide (LC50 = 0.22 mg L-1 ). Interestingly, compound E3 also displayed potent insecticidal activity against Pyrausta nubilalis (LC50 = 0.182 mg L-1 ) and Chilo suppressalis (LC50 = 0.64 mg L-1 ), and the LC50 values of fluxametamide were 0.23 mg L-1 (P. nubilalis) and 2.26 mg L-1 (C. suppressalis), respectively. The molecular docking results revealed that the compound E3 can form a hydrogen bond and two Pi-Pi bonds with the active sites of GABA receptors. In addition, the DFT calculations were also performed to study the relationship between insecticidal activities. The structure-activity relationships suggested that the identity of the R substituent was crucial for their pesticidal activities. The results of the present study suggest that isoxazoline acylhydrazone derivatives could be promising candidates against P. xylostella and other Lepidopteran pests. © 2023 Society of Chemical Industry.

Design, Synthesis, Biological Evaluation, and Molecular Docking Studies of 4‐Nitrobenzohydrazide Derivatives as Potential Anticancer Agents

AbstractA series of new acylhydrazone derivatives were synthesized from the condensation of different substituted salicylaldehydes with 4‐nitrobenzohydrazide at a molar ratio of 1 : 1 in a one‐step reaction. These compounds have been characterized by spectroscopic techniques such as FT‐IR, NMR, ESI‐MS and CHN analysis. All compounds were examined for anticancer activity in three cancer cell lines viz. melanoma (A375), colon (HT‐29) and lung (A549). Compound 3 exhibits good cytotoxicity activity with an IC50 value of 0.38±0.08 μM against A375 and compound 2 exhibits better cytotoxicity 1.34±0.02 μM and 1.48±0.04 μM against HT‐29 and A549, respectively. Similarly, other compounds have also shown significant cytotoxicity activity against three cell lines. The cytocompatibility assay on the normal mouse fibroblast cell line (L929) and the hemolysis assay on human red blood cells were used to confirm the nontoxic activity. DAPI(4′,6‐diamidino‐2‐phenyliindole) staining experiments demonstrated that compounds induced apoptosis in the A375 cell line. Further, in silico molecular docking was performed against three various targets. In silico studies demonstrated that compounds 1(ΔGb=−9.3 kcal/mol), 2 (ΔGb=−8.8 kcal/mol), and compound 3(ΔGb=−9.0 kcal/mol) have a good binding energy score with an active pocket of protein inhibitor kinases. The outcomes of the current study showed that these compounds have anticancer action and might be used to create more potent drugs to treat melanoma, colon, and lung cancers.

Photoinduced Crystal-to-Liquid Transition of Acylhydrazone-Based Photoswitching Molecules.

A photoinduced crystal-to-liquid transition (PCLT) behavior of new acylhydrazone derivatives (NCs) is reported. The photoswitching of the NCs was identified as a negative photochromism with a high E-to-Z conversion yield (>98%). A kinetic analysis shows a half-life of almost one month. Owing to these high photoswitching performances, we successfully isolated both E- and Z-forms, evaluated their crystal structures, and observed distinct thermal behaviors. The Z-form melts at a lower temperature than the E-form by several tens of degrees. The PCLT occurs at even lower temperatures. UV irradiation induces the E-to-Z conversion in the crystalline state, thereby inducing a eutectic melting. In addition to the PCLT, we observed a photomechanical behavior of the crystals, which suggests that the presented acylhydrazones can be new members of the photoresponsive crystalline materials.

Design, synthesis, in silico ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives

Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using 1H-NMR, 13C-NMR, IR, and Mass spectroscopy. Among analogs, compound 5h bearing furan ring with IC50=8.94 μM was more potent than kojic acid (IC50=16.68 μM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound 5h was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound 5h, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for 5 g and 5h were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the 5h is a soft molecule and ready for chemical reaction with other interacting molecules. Communicated by Ramaswamy H. Sarma

Discovery of rosin-based acylhydrazone derivatives as potential antifungal agents against rice Rhizoctonia solani for sustainable crop protection.

The use of fungicides to protect crops from diseases is an effective method, and novel environmentally friendly plant-derived fungicides with enhanced performance and low toxicity are urgent requirements for sustainable agriculture. Two kinds of rosin-based acylhydrazone compounds were designed and prepared. Based on the antifungal activity assessment against Rhizoctonia solani, Fusarium oxysporum, Phytophthora capsici, Sclerotinia sclerotiorum, and Botrytis cinerea, acylhydrazone derivatives containing a thiophene ring were screened and showed an inhibitory effect on rice R. solani. Among them, Compound 4n, with an electron-withdrawing group on the benzene ring structure attached to the thiophene ring, showed optimal activity, and the EC50 value was 0.981 mg L-1 , which was lower than that of carbendazim. Furthermore, it was indicated that 4n could affect the mycelial morphology, cell membrane permeability and microstructure, cause the generation of reactive oxygen species in fungal cells, and damage the nucleus and mitochondrial physiological function, resulting in the cell death of R. solani. Meanwhile, Compound 4n exhibited a better therapeutic effect on in vivo rice plants. However, the induction activity of 4n on the defense enzyme in rice leaf sheaths showed that 4n stimulates the initial resistance of rice plants by removing active oxygen, thereby protecting the cell membrane or enhancing the strength of the cell wall. Through the quantitative structure-activity relationship study, the quantitative chemical and electrostatic descriptors significantly affect the binding of 4n with the receptor, which improves its antifungal activity. This study provides a basis for exploiting potential rosin-based fungicides in promoting sustainable crop protection. © 2022 Society of Chemical Industry.

Design, synthesis, and cytotoxicity evaluation of novel indole-acylhydrazone derivatives of 4-pyridinone as potential histone deacetylase-2 inhibitors.

Histone deacetylation is one of the essential cellular pathways in the growth and spread of cancer, so the design of histone deacetylase (HDAC) inhibitors as anticancer agents is of great importance in pharmaceutical chemistry. Here, a series of indole acylhydrazone derivatives of 4-pyridone have been introduced as potential histone deacetylase inhibitors. Seven indole-acylhydrazone-pyridinone derivatives were synthesized via simple, straightforward chemical procedures. The molecular docking studies were accomplished on HDAC2 compared to panobinostat. The cytotoxicity of all derivatives was studied on MCF-7 and MDA-MB-231 breast cancer cell lines by MTT assay. Molecular docking studies supported excellent fitting to the HADC2 active site with binding energies in the range of -10 Kcal/mol for all derivatives. All compounds were tested for their cytotoxicity against MCF-7 and MDA-MB-231 cell lines; derivatives A, B, F, and G were the best candidates. The half-maximal inhibitory concentration (IC50) values on MCF-7 were below 25 mg/mL and much lower than those obtained on the MDA-MB-231 cell line. The derivatives showed selectivity toward the MCF-7 cell line, probably due to the higher HDAC expression in the MCF-7 cell line. In this regard, debenzylated derivatives F and G showed slightly better cytotoxicity, which should be more studied in the future. Derivatives A, B, F, and G were promising for future enzymatic studies.

Synthesis, structural characterization, and antimicrobial activity of novel ferrocene-N-acyl hydrazones designed by means of molecular simplification strategy Celebrating the 100th anniversary of the birth of Professor Paulo Freire

• A new series of ferrocenyl- N -acyl hydrazone (Fc-NAH) derivatives has been planned by means of a molecular simplification strategy. • The CeCl 3 -catalyzed synthesis of the N -acyl hydrazone moiety has led to the stereoselectivity of the E -isomers . • The new more structurally simple compounds Fc-NAH have disclosed an interesting antimicrobial profile, while the starting model molecules were inactive. • Compounds Fc-NAH have been evaluated for their antimicrobial activity and exhibited especially good outcomes against Gram-positive bacteria. The pursuit of new biological active and structurally diverse molecules is the main core of medicinal chemistry, which can be achieved by means of different theoretical and experimental strategies, including molecular simplification. Starting from a structural model of more complexity, it is possible to design new molecules with easier synthetical requirements, improved physicochemical properties, and even new biological profiles. Based on this strategy, 36 ferrocenyl- N -acyl hydrazone (Fc-NAH) hybrids have been planned, synthesized, and screened for their antimicrobial activity. The applied synthetical method has led to the stereoselectivity of the E -isomers, avoiding diastereomeric mixtures that can affect biological studies. In opposition to the starting structural model, the Fc-NAH derivatives have disclosed significant antimicrobial activity. Compounds SintMed(75-110) were especially active against the gram-positive bacterial strains B. subtilis and S. aureus , and the nitro-substituted derivatives must be highlighted due to their best results. In fact, derivatives SintMed77 (3,5-dinitrophenyl) and SintMed93 (4-nitrophenyl) were the most active in the series, with inhibitory zones of 20.1 ± 0.52 and 21.4 ± 0.83, respectively. General structural features could be established from the analysis of the in vitro antimicrobial activity and minimum inhibitory concentration (MIC) studies, such as the importance of the electron-withdrawing substituents, as well as the role of the formation of hydrogen bonds in the biological responses. Besides, a clear tendency of low activity or even inactivity was observed for the derivatives bearing nonpolar groups, a piece of crucial information for further studies of structural modifications. By means of molecular simplification strategy, a new series of ferrocenyl- N -acyl hydrazones (Fc-NAH) was planned, synthesized, and found to be active as antimicrobials, in opposition to the inactive starting more complex model.

Synthesis of Emodin Acylhydrazone Derivatives and Determination of Vibrio harveyi Inhibitory Activity

Synthesis of Emodin Acylhydrazone Derivatives and Determination of Vibrio harveyi Inhibitory Activity

Influenza A Virus Neuraminidase Inhibitors.

Depending on the strain, influenza A virus causes animal, zoonotic, pandemic, or seasonal influenza with varying degrees of severity. Two surface glycoprotein spikes, hemagglutinin (HA) and neuraminidase (NA), are the most important influenza A virus antigens. NA plays an important role in the propagation of influenza virus by removing terminal sialic acid from sialyl decoy receptors and thereby facilitating the release of viruses from traps such as in mucus and on infected cells. Some NA inhibitors have become widely used drugs for treatment of influenza. However, attempts to develop effective and safe NA inhibitors that can be used for treatment of anti-NA drugs-resistant influenza viruses have continued. In this chapter, we describe the following updates on influenza A NA inhibitor development: (i) N-acetylneuraminic acid (Neu5Ac)-based derivatives, (ii) covalent NA inhibitors, (iii) sulfo-sialic acid analogs, (iv) N-acetyl-6-sulfo-β-D-glucosaminide-based inhibitors, (v) inhibitors targeting the 150-loop of group 1 NAs, (vi) conjugation inhibitors, (vii) acylhydrazone derivatives, (viii) monoclonal antibodies, (ix) PVP-I, and (x) natural products. Finally, we provide future perspectives on the next-generation anti-NA drugs.

Synthesis and Biological Activity of Aldehyde Derivatives of Isopimaric Acid

Four series of acylhydrazone derivatives, including halogenated aryl modified acylhydrazone, thiophene, pyrrole and quinoline, were synthesized and characterized. The minimum inhibitory concentrations of the compounds against five bacteria were determined and most of the compounds displayed some degree of antibacterial activity. Isopimaric acid (pyrrole-3-carboxaldehyde) acylhydrazone (3j) exhibited the most potent activity against Streptococcus pneumonia and Klebsiella Pneumonia, with the minimum inhibitory concentration being 3.91 μg/mL. The antimicrobial activity against S. pneumoniae was improved when the pyrrole structure was introduced into isopimaric acid. All heterocyclic acylhydrazone derivatives of isopimaric acid exhibited a good in vitro antitumorial activity at 100 μM. It is concluded that the inhibitory effect of isopimaric acid (2-fluoro-6-methoxybenzaldehyde) acylhydrazone (3d) on Hep G2 and isopimaric acid (3-bromothiophene-2-carbaldehyde) acylhydrazone (3g) on Hep G2 and MDAMB 231 is better than that of the positive control 5-fluorouracil (5-FU) (76.51%), which is a widely used clinical anticancer agent, at 100 μM.

Design, synthesis and protein-binding character of an acylhydrazone anticancer candidate

Acylhydrazone derivatives have potential antitumor activities due to their metabolic modulation effect in cancer cells. Herein, an acylhydrazone compound, p-nitrobenzaldehyde-p-methylbenzoylhydrazone (MNB), was designed, prepared and characterized. The interaction of MNB with carrier protein is systematically deciphered using spectroscopic, electrochemical and modeling techniques. Ultraviolet (UV) and electrochemical impedance spectroscopy (EIS) indicate that MNB can couple with albumin through hydrophobic interaction. Molecular probe experiments reveal MNB is located at Sudlow's site I in albumin. Stern-Volmer equation, Langmuir adsorption isotherm, van’t Hoff equation and Arrhenius equation are applied to analyze the thermodynamic and kinetic characteristics of the interaction. The results demonstrate that the interaction is a typical spontaneous process dominated by entropy, whose activationenergy is ca. 26.78 kJ·mol−1. Circular dichroism (CD) spectra show that MNB has a small impact on the conformation of albumin. Molecular docking investigation simulates the structural details of the new complex, which is consistent with experimental conclusions. This study provides comprehensive information on the interaction of MNB with carrier protein, which lays the basis for its application as a new anticancer candidate.

Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives.

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

A novel acyl hydrazone schiff’s bases of benzimidazole-2-thiol

A series of novel acyl hydrazone derivatives of benzimidazole-2-thiol were synthesized. The acylhydrazide was condensed with a series of aromatic substituted aldehydes to yield the tetra decylhydrazone Schiff”s bases of benzimidazole-2-thiol. The acylhydrazide was taken in methanol in round bottom flask added 2-3 drops acetic acid and refluxed on hotplate the reaction mixture was monitored with TLC. After completion of reaction the product was precipitated in ice cool water, washed and dried. The synthesized compounds were screened for different biological activities such as antimicrobial, antihistamine, neutropic, analgesic, antiprotozoal, antimalarial, antiallergic, antioxidant, anticonvulsant, anti-tubercular and have shown a good results.