Hydrazide-hydrazone Derivatives Research Articles

Novel hydrazide-hydrazone containing 1,2,4-triazole as potent inhibitors of antiapoptotic protein Bcl-xL: Synthesis, biological evaluation, and docking studies.

This study describes the synthesis and characterization of a series of novel hydrazide-hydrazone derivatives containing a 1,2,4-triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT-116, HepG-2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl-xL inhibitory concentration (IC50) values. These compounds further demonstrated selective cytotoxicity against the Bcl-xL-dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl-xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl-xL. Overall, these results demonstrate the potential of these novel hydrazide-hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5-fluorouracil.

New hydrazide-hydrazone derivatives containing coumarin and indole moiety: Synthesis, spectroscopic characterization and DFT studies

Two new compounds (3 and 4), coumarin indole derivatives with a hydrazide-hydrazone skeleton, were synthesized, and their spesctroscopic properties, including UV-vis, FTIR, and 1H-13C NMR were investigated experimentally and theoretically. The experimental data and DFT (density functional theory) results of the compounds matched well and showed good agreement. Moreover, the DFT/B3LYP/6-311G++(2d,p) calculations were utilized to perform HOMO and LUMO energy, net atomic charges, MEP surface, and NBO analysis for the optimized geometries of 3 and 4. NBO analysis revealed that the synthesized compounds exhibit high molecular stability because of significant hyperconjugative interactions. The experimental and theoretical band gaps (ΔEg) investigated in some organic solvents with different polarities were determined to be in the range of 2.68-2.75 eV and 3.22-3.25 eV for compound 3, and 2.69-2.77 eV and 3.41-3.47 eV for compound 4, respectively. The compounds demonstrated thermal stabilities with a Td value higher than 300 °C.

Ecofriendly Synthesis, Spectroscopic Analysis and in silico Study of Coumarin Hydrazide-Hydrazone Derivative Targeted against HIV and SARS-CoV-2

Ecofriendly Synthesis, Spectroscopic Analysis and in silico Study of Coumarin Hydrazide-Hydrazone Derivative Targeted against HIV and SARS-CoV-2

Hydrazide–hydrazones as potential antitubercular agents: overview of the literature (1999-2023)

Hydrazide-hydrazone derivatives are prevalent in numerous bioactive compounds, showcasing a diverse array of biological effects including antibacterial, antitubercular, antifungal, anticancer, anti-inflammatory, anticonvulsant, antiviral, and antiprotozoal properties. Consequently, numerous medicinal chemists undertake the synthesis of various hydrazide-hydrazones, subjecting them to evaluation for their biological activities. Among these, antituberculosis activity stands out as a recurring focus in scientific literature. This paper provides a comprehensive overview of research spanning the last twenty-four years (1999-2023), concentrating on the antituberculosis properties of hydrazide-hydrazone derivatives. The insights presented herein could serve as a valuable roadmap for the development of novel hydrazide-hydrazones with potential antimicrobial efficacy.

Design and synthesis of bis(indolyl)-hydrazide-hydrazone derivatives and their antifungal activities against plant pathogen fungi

A series of bis(indolyl)-hydrazide-hydrazone derivatives were synthesised, and their structures were characterised using 1H-NMR and HRMS. The antifungal activity of the prepared compounds was evaluated against Pyricularia oryzae Cav., Colletotrichum ­gloeosporioides Penz., Botrytis cinerea Pers.: Fr. and Rhizoctonia solani Kühn using the mycelial growth rate method. The preliminary bioassays revealed that most of the synthesised compounds exhibited antifungal activity against the four tested fungi and displayed a remarkable inhibitory effect on the mycelium growth of R. solani. In particular, compounds 3b, 3c, and 3k demonstrated significant antifungal activity against R. solani, with EC50 values of 26.42, 20.74, and 22.41 μM, respectively, outperforming the positive control shenqinmycin (47.18 μM) and carvacrol (49.13 μM).

Evaluation of Antimicrobial Efficacy of Hydrazide-Hydrazone Derivatives against Food Borne Pathogens

Evaluation of Antimicrobial Efficacy of Hydrazide-Hydrazone Derivatives against Food Borne Pathogens

Novel Hydrazide Hydrazone Derivatives as Antimicrobial Agents: Design, Synthesis, and Molecular Dynamics

Ester 2 was produced by reacting thiourea derivative 1 with ethyl 2-chloro-3-oxobutanoate in MeOH containing piperidine. Hydrazide 3 was produced by reacting the latter ester with hydrazine hydrate in EtOH at reflux. By reacting hydrazide 3 with aromatic/heterocyclic aldehydes, twelve derivatives of hydrazide hydrazone 5a–l were produced. Spectral measurements and elemental analysis verified the molecular structure. Compounds 2, 5a, 5c, 5d, and 5f had strong effects on all the pathogenic bacterial strains according to an evaluation of the antimicrobial qualities of the synthetic compounds. With inhibitory zone diameters ranging from 16 to 20.4 mm, hydrazide hydrazone 5f exhibited the strongest activity. Additionally, the minimum inhibitory concentration (MIC) was assessed. The best outcomes were found with hydrazones 5c and 5f. For B. subtilis, the MIC of 5c was 2.5 mg/mL. For E. coli and K. pneumoniae, the MIC of 5f was 2.5 mg/mL. The molecular mechanics-generalized born surface area (MM/GBSA) was utilized to compute binding free energies via a molecular dynamics simulation analysis of the most active compounds, 5f and 5c. Moreover, computational analyses demonstrated that 5f had a substantial affinity for the active site of DNA gyrase B, suggesting that this compound could be a strong platform for new structure-based design efforts.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide–hydrazone derivatives of 3,4-dihydroxyphenylacetic acid

A series of novel Schiff base derivatives (1–28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI–MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Exploring etofenamate hydrazide-hydrazone/copper(II) complexes: Synthesis, anticancer activity, carbonic anhydrase IX inhibition and docking studies

Hydrazide-hydrazone derivatives have garnered significant interest from researchers globally due to their wide range of biological activities, including antiviral, anticancer, and anti-inflammatory properties. In this study, a novel series of etofenamate hydrazide-hydrazone compounds (2a-2s) and their Cu(II) complexes (3a-3s) were designed and synthesized. The compounds were characterized using various analytical techniques such as FT-IR, 1H NMR, 13C NMR, MS, and elemental analysis. Additionally, the compound 2c and Cu(II) hydrazone complex 3a were further characterized using single X-ray crystallography. The anti-proliferative activity of the compounds was evaluated against Ishikawa human endometrial cancer cell line and non-tumour L929 cells using MTT assay. Additionally, the apoptotic potential of the compounds was investigated through caspase-3 activity, Bax and Bcl-2 gene expression analysis, and annexin-V binding. Furthermore, carbonic anhydrase IX activity and in silico studies were conducted to elucidate the mechanism of action. Overall, compound 3s demonstrated significant antiproliferative effects with an IC50 value of 0.27±0.01 µM against Ishikawa cells.

Evaluation of Cytotoxicity and Apoptosis Induced by Coumarin Hydrazide-Hydrazone Derivatives in Human Hepatocellular Carcinoma Cell Line

Coumarin and aryl hydrazide-hydrazone have attracted our attention due to their vast biological properties. Previous studies suggested that coumarin-tethered aryl hydrazide-hydrazone showed potent activities against HepG2. In the present study, we investigated the cytotoxic potency of the coumarin derivatives 1 - 3 to compare with coumarin hydrazine-hydrazone hybrids 4 and 5 against hepatocellular carcinoma HepG2 and LH86 cell lines. Among the tested coumarins, hybrids 4 and 5 showed highly potent activity against HepG2 with IC50 values of 17.82 ± 2.79 and 7.87 ± 0.88 𝜇g/mL, respectively. The hybrid 4 also showed the strongest activity against LH86 cell line with IC50 values of 48.32 ± 2.64 𝜇g/mL. Further, we have studied the mechanism of action of the hybrid compounds 4 and 5 in HepG2 cells via the flow-cytometry analysis and the activation of the caspase-3 and caspase-7. The results showed that hybrids 4 and 5 obviously inhibited the proliferation of HepG2 cell line through inducing apoptosis. HIGHLIGHTS Focusing on coumarin and aryl hydrazide-hydrazone possess significant biological properties. We reported the preparation of coumarin hydrazine-hydrazone hybrids and evaluated their effects against hepatocellular carcinoma cell lines HepG2 and LH86. The hybrid compounds exhibited high potency against HepG2 and LH86. Flow-cytometry and caspase-3/7 expression analysis revealed that the hybrid compounds induced apoptosis in HepG2 cells. GRAPHICAL ABSTRACT

Synthesis of Some New Hydrazide-Hydrazone and 2-Pyridone Derivatives of Potential Biological Interest

A series of new2-pyridone derivatives was synthesized through reaction of the a,?-unsaturated carbonyl compounds with malononitrile in refluxing ethanolin basic media. The a,?-unsaturated carbonyl compounds were synthesized from the reaction of the hydrazide-hydrazone with substituted benzaldehydes in presence of ethanol, and triethylamine as a base. Hydrazide-hydrazone derivative was prepared by reactions 2-cyanoacetohydrazide with4- benzylsulfonylacetophenonein refluxing ethanol. The structures of all synthesized compounds were confirmed by spectral (FT-IR, 1H NMR, 13C NMR) data.. KEYWORDS :4-(Benzylthio) acetophenone, 4-Benzylsulfonylacetophenone, 2-Cyanoacetohydrazide, Hydrazide-hydrazone, 2-Pyridone derivatives, a,?-unsaturated carbonyl compounds.

Synthesis, DFT Study, and In Vitro Evaluation of Antioxidant Properties and Cytotoxic and Cytoprotective Effects of New Hydrazones on SH-SY5Y Neuroblastoma Cell Lines.

A series of ten new hydrazide-hydrazone derivatives bearing a pyrrole ring were synthesized and structurally elucidated through appropriate spectral characteristics. The target hydrazones were assessed for radical scavenging activity through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) tests, with ethyl 5-(4-bromophenyl)-1-(2-(2-(4-hydroxy-3,5-dimethoxybenzylidene)hydrazine-yl)-2-oxoethyl)-2-methyl-1H-pyrrole-3-carboxylate (7d) and ethyl 5-(4-bromophenyl)-1-(3-(2-(4-hydroxy-3,5-dimethoxybenzylidene) hydra zine-yl)-3-oxopropyl)-2-methyl-1H-pyrrole-3-carboxylate (8d) highlighted as the best radical scavengers from the series. Additional density functional theory (DFT) studies have indicated that the best radical scavenging ligands in the newly synthesized molecules are stable, do not decompose into elements, are less polarizable, and with a hard nature. The energy of the highest occupied molecular orbital (HOMO) revealed that both compounds possess good electron donation capacities. Overall, 7d and 8d can readily scavenge free radicals in biological systems via the donation of hydrogen atoms and single electron transfer. The performed in vitro assessment of the compound's protective activity on the H2O2-induced oxidative stress model on human neuroblastoma cell line SH-SY5Y determined 7d as the most perspective representative with the lowest cellular toxicity and the highest protection.

Synthesis, Characterization, 'ADMET-SAR' Prediction, DPPH Assay, and Anti-Mycobacterium Study of 4-[(substituted benzyl) amino]benzo hydrazides and its Hydrazones as the Acyl-CoA Carboxylase, AccD5 Inhibitors.

Hydrazide-hydrazone derivatives have shown diverse biological activities, such as antitubercular (anti-TB), antibacterial, antifungal, anticancer, anti-inflammatory, antiviral, and antiprotozoal actions. Hydrazide-hydrazones contain azomethine (-NH-N=CH-) group connected with carbonyl group and are believed to be responsible for various pharmaceutical applications. They aid in the synthesis of different five-membered heterocyclic systems, such as oxadiazole, triazoles, etc. Methods: In the present study, various hydrazines/hydrazones were synthesized starting from 4- amino benzoic acid derivatives. Structures of all 9 newly synthesized compounds (6a-6d and 8a- 8e) were further characterized by using various spectroscopic methods, such as 1H-NMR (Nuclear Magnetic Resonance), FT-IR (Fourier-transform infrared spectroscopy), Gas chromatographymass spectrometry (GC-MS), etc. Furthermore, molecular docking analysis against the acyl-CoA carboxylase, AccD5 (PDB ID: 2A7S), was also carried out using the Glide module, which depicted good binding scores than standard drugs. The anti-tuberculosis activity of all the hydrazides and hydrazones (6a-6d and 8a-8e) were evaluated against the Mycobacterium tuberculosis H37 RV strain using the Alamar-Blue susceptibility (MABA) test. The activity was expressed as the minimum inhibitory concentration (MIC) in μg/mL values. The antioxidant activity was also carried out using a DPPH assay. Our findings demonstrated highly encouraging in-vitro results (MABA assay, MIC: 1.2 μg/mL) of hydrazones as depicted by good antimycobacterial activity. The antioxidant results showed a moderate to a good percentage of DPPH inhibition. Our in-silico ADMET analysis further suggested good pharmacokinetic and toxicity-free profiles of synthesized analogues (6a-6d and 8a-8e). Our results signify hydrazones/hydrazines as potential hit candidates against the future developments of potent and safer anti-TB agents.

Analgesic properties of newly synthesized N pyrrolyl hydrazide hydrazones

Purpose: To screen a series of newly synthesized N-pyrrolyl hydrazide hydrazones for analgesic activity via Paw-pressure (PP) test and hot plate test (HPT).
 Methods: The compounds newly synthesized through the classical Paal-Knor cyclization, N-pyrrolyl hydrazide-hydrazones were administered intraperitoneally at a dose of 20 mg/kg. Paw pressure and hot plate tests were applied to assess the analgesic properties. In addition, stress-induced analgesia with naloxone as a non-selective opioid receptor antagonist was performed.
 Results: The compound (DI-5g), containing an izatine carbonyl fragment, was the most promising. It presented the highest paw pressure threshold (25 AU at 30th min) by exceeding the analgesic activity of the referent metamizole (23 AU at 30th min). The relative effect from the hot plate test was consistent with the paw pressure results. Opioid receptors were involved in the analgesic activities of N-pyrrolyl hydrazide-hydrazones.
 Conclusion: The N-pyrrolyl carboxylic acids are synthesized and identified as new compounds and their hydrazide-hydrazone derivatives as promising leads for future design and synthesis of drugs with possibly prolonged analgesic activity.

Investigation of Antimicrobial Activity of Some Ethylparaben Hydrazide-Hydrazone Derivatives.

The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules. In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 μg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 μg/mL against Staphylococcus aureus strain (ATCC 29213). Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.

Design, synthesis, antioxidant and anticholinesterase activities of novel isonicotinic hydrazide-hydrazone derivatives

The design and synthesis of hydrazone derivatives are increasing in popularity day by day due to the significant biological activities of this scaffold. In the present study, twelve novel isonicotinic hydrazide-hydrazone analogues were synthesized by the condensation reaction of isonicotinic hydrazide with benzaldehyde possessing sulfonate moiety. The structures of the novel compounds have been characterized in detail using spectroscopic techniques. All compounds have shown inhibitory effects against the AChE enzyme at rates ranging from 21.00 to 59.48%. Among them, compound 5 has exhibited the best inhibitory effect of 59.48% against AChE at a concentration of 0.1 mM. Furthermore, to determine how effective the novel compounds are as antioxidants, FRAP and DPPH studies were also carried out. FRAP values in compounds 1–12 were found to range from 26.989–3415.556 µmol FeSO4.7H2O/mg. They also displayed moderate antioxidant potential in the range of SC50=0.03–87.32 mg/mL compared with the control Trolox (SC50 =0.004) in DPPH radical scavenging activities. It was seen that the AChE inhibition percentages of the compounds were in the range of 23.04–58.10% at 0.1 mM concentration. This is the first research on the synthesis, antioxidant and enzyme inhibition properties of these compounds.

Synthesis, structure elucidation and in vitro microsomal metabolism of adamantane hydrazide-hydrazone derivatives

Synthesis, structure elucidation and in vitro microsomal metabolism of adamantane hydrazide-hydrazone derivatives

Synthesis and Biological Evaluation of Some Hydrazide-Hydrazone Derivatives as Anticancer Agents

In this study, a series of hydrazide-hydrazone derivatives (3a-3u) were synthesized and evaluated for their anticancer activities against prostate cancer cell line (PC-3), breast cancer cell line (MCF-7), colon cancer cell line (HT-29) and human umbilical vein endothelial cells (HUVEC) using MTT assay. In particular, compound 3h having a pyrrole ring was found to be the most potent derivative with IC50 = 1.32, 2.99, 1.71 µM against PC-3, MCF-7, HT-29 cancer cell lines respectively using paclitaxel as a standard compound. Furthermore, compound 3h was subjected to further biological studies such as caspase-3 activity and Annexin-V assay to evaluate their inhibitory potentials. The activity results displayed that compound 3h increased caspase-3 activation and the number of cells to early apoptosis. The additional studies like pharmacokinetics, bioavailability scores and drug-likeness properties were also evaluated. The in silico pharmacokinetics predictions displayed that the bioavailability of these compounds may be high.

Coumarin Hydrazide: Chemistry, Synthesis and Pharmacological Activities - A Review

Coumarins are heterocyclic compound with a benzopyrone structure. Coumarins are a large group of organic compounds found in several plants even in bacteria and fungi. The biological activities of coumarins and its derivatives includes anticoagulant, anticancer, antiulcer, antifungal, anti-HIV, antimicrobial, antiosteoporosis, antioxidant and anti- inflammatory activity. Hydrazide-hydrazone derivatives act as structural sub units in many pharmacologically active compounds including coumarins to give biological activities like antimicrobial, anticancer, antifungal, anti-inflammatory, antiviral, anti-tubercular, and antiprotozoal activity. The interest in the synthesis of coumarin derivatives has been gaining importance over the last decades, reflecting the importance of such compounds in both medical and chemical research. In this review hydrazide-hydrazone derivatives of coumarins are taken into consideration and emphasised on the anticancer, antitubercular, antimicrobial, antioxidant and antidiabetic activity of these derivatives. Keywords: Coumarin, hydrazide, heterocyclic, benzopyran, antitumor, antimicrobial, antioxidant

Synthetic Transformation of 2-{2-Fluoro[1,1'-biphenyl]-4-yl} Propanoic Acid into Hydrazide-Hydrazone Derivatives: In Vitro Urease Inhibition and In Silico Study.

In the present study, 28 acyl hydrazones (4-31) of flurbiprofen were synthesized in good to excellent yield by reacting different aromatic aldehydes with the commercially available drug flurbiprofen. The compounds were deduced with the help of different spectroscopic techniques like 1H-NMR and HREI-MS and finally evaluated for in vitro urease inhibitory activity. All of the synthesized products demonstrated good inhibitory activities in the range of IC50 = 18.92 ± 0.61 to 90.75 ± 7.71 μM as compared to standard thiourea (IC50 = 21.14 ± 0.42 μM). Compound 30 was found to be the most active among the series better than the standard thiourea. A structure-activity relationship (SAR) study revealed that the presence of electron-donating groups on the phenyl ring plays a prominent role in the inhibition of the urease enzyme. Moreover, in silico molecular modeling analysis was carried out to study the effect of substituents in synthesized derivatives on the binding interactions with the urease enzyme.