Schiff Base Derivatives Research Articles

Design, Synthesis, and Anti-Mycobacterial Evaluation of Triclosan-Isoniazid Hybrids.

A series of Triclosan-based hybrids and their Schiff base derivatives with isoniazid were designed through in silico modelling and synthesized using copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction. These compounds were then evaluated against both Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mab). However, none of the synthesized hybrids exhibited significant growth inhibition, with minimum inhibitory concentration (MIC) values consistently exceeding 100 µg/mL. To further investigate these findings, we conducted mechanistic studies including thermogravimetric analysis (TGA) and UV-Vis stability tests. TGA demonstrated thermal stability of the Schiff bases up to 270 °C, while UV-Vis analysis confirmed their chemical resilience across a wide pH spectrum, showing resistance to hydrolysis under acidic and basic conditions. The lack of observed antimicrobial activity may be attributed to the high lipophilicity of these molecules, as indicated by LogP values exceeding 5, which could limit their bioavailability. These findings suggest that although combining triclosan and isoniazid holds potential, further optimization of this hybrid strategy is necessary to improve efficacy.

Synthesis, spectroscopic characterization techniques of aromatic iminoaniline derived compound, along with the evaluation of its LNO properties using quantum chemistry

In this research work, we synthesized a Schiff base derivative, N,N-dimethyl-4-{[(4-nitrophenyl)imino]-methyl}aniline, denoted as (n1). The molecule (n1) was characterized using spectroscopic analyses, including FT-IR, NMR 1H, and 13C. Our compound (n1) is an unsaturated molecule, consisting of two benzylic rings connected by a methylimine bridge. The resulting system comprises seven alternating π bonds. At both ends of (n1) and in the para position, there are the N(CH3)2 group with a strong electron-donating effect and the NO2 group with a strong electron-accepting effect. The molecular structure of our compound prompted us to evaluate and study its properties in the field of NLO. The assessment of NLO properties is conducted by determining the Egap and employing density functional theory (DFT) quantum chemistry studies. The optical gap of (n1), measured using the Tauc method, is found to be 2.7 eV, serving as a reference value for the choice of the DFT functional in theoretical calculations. Quantum chemistry studies were carried out using Gaussian09 software, and the results were visualized with GaussView05. CAM-B3lyp functional was chosen for theoretical calculations due to its close agreement with experimental values. The studies confirm that (n1) exhibits significant NLO properties. Additionally, NBO (Natural Bond Orbital) analyses provide insight into the mechanism and trajectory of intramolecular charge transfer in (n1).

Synthesis and Molecular Docking Study of Hydrazone Schiff Bases of α‐Naphthalene‐Containing Alkyl Phenyl Ether Fragment as Potent α‐Amylase and α‐Glucosidase Inhibitors

AbstractIn this study, new Schiff base derivatives of α‐naphthalene acetic acid containing alkyl phenyl ether fragment have been effectively synthesized through multistep reaction process, characterized by 1H‐NMR and 13C‐NMR spectroscopy. These derivatives have been tested for their in vitro α‐amylase and α‐glucosidase inhibitory activities. In the series, 8 compounds (2j, 2f, 2e, 2m, 2a, 2b, 2l, and 2c) exhibited promising α‐amylase inhibition with IC50 values from 5.38 ± 0.36 to 14.59 ± 0.64 µg/mL. Similarly, in the case of α‐glucosidase inhibitory activity, 10 derivatives (2e, 2f, 2j, 2m, 2b, 2c, 2i, 2d, 2a, and 2l) exhibited excellent activity having IC50 values from 6.96 ± 0.39 to 16.27 ± 0.31 µg/mL, wheras the remaining derivatives exhibited good‐to‐least antidiabetic potential. The ADME properties were calculated for all Schiff base derivatives using Swiss‐ADME web tool. Furthermore, the docking studies identified the binding modes of the compounds.

Design, Synthesis, and In-Silico Analysis of Thiazole-Embedded Schiff Base Derivatives for Breast Cancer Therapeutic Potential

Thiazole-derived Schiff base compounds possess significant pharmacological properties, influencing various enzymes in metabolic pathways and exhibiting antibacterial, antifungal, anti-inflammatory, antioxidant, and antiproliferative activities. This study delves into the synthesis, characterization, and in-silico analysis of ten thiazole-embedded Schiff base derivatives (TZ1-10), benchmarking them against five Food and Drug Administration (FDA)-approved breast cancer drugs. Molecular docking against multiple therapeutic targets related to fatty acid synthase and cell proliferation (PDB IDs: 4FX3, 4OAR, 3NUP, and 3ERT) alongside ADME and Lipinski rule assessments were conducted. Compounds TZ6 and TZ8 emerged as promising candidates with docking scores of -8.0 kcal/mol and -8.2 kcal/mol respectively against the 4FX3 protein. These findings contribute to a deeper understanding of thiazole-embedded Schiff base derivatives, showcasing their potential for future medicinal and scientific applications.

Design, synthesis and antibacterial activity of new Isatin-based Schiff base derivatives: Molecular docking, POM analysis, in silico pharmacokinetics and identification of antitumor pharmacophore sites

In this study,we have reported a series of Isatin-based Schiff base derivatives G(1–5), the formation of the synthesized compounds was confirmed by Spectro analytical techniques. The synthesized compounds were screened for antimicrobial activity against Pseudomonas aeruginosa, Salmonella typhie,andStaphylococcus aureusbacterial strainsandantifungalscreening againstCandida albicansusing disc diffusion and broth microdilution with ciprofloxacin and fluconazole as reference standards, which indicated that the studied compounds exhibited exceptional antibacterial properties. The density functional theory (DFT) studies were used to study atomic structure and reactivity, including absolute electronegativity (χ), electrophilicity (ω), electron acceptor (ω+), donor capabilities (ω–), electron affinity (EA), energy gap (∆E), global hardness (η), global softness (S), and ionization potential (IP) and frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and Mulliken Charge analysis. The Petra, Osiris, and Molinspiration(POM) tests found three integrated pharmacophore sites with antibacterial, antiviral, and anticancer activities. Molecular docking studies are also used to determine theaffinity and mode of action of the synthesized compounds with the targeted receptor, Staphylococcus aureus nucleoside diphosphate kinase receptor, which supported the experimental results. In silico analysis of thermodynamic and therapeutic effectiveness properties, including Lipinski's 'rule of five', Veber's rule, boiled egg model, and ADME properties, forecastthetoxicity-free, non-carcinogenic, and risk-free oral administration of the synthesized complexes.

Synthesis of Sulfonamide-Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies.

The current study focuses on the synthesis and characterization of six benzenesulfonamide-based Schiff base derivatives (7-12) with various electron-withdrawing and electron-donating substituents (-F, -CI, -Br, -CH3, and -OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7-12) were elucidated by elemental analysis and FT-IR, 1D (1H, 13C, APT, and DEPT-135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7-12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032-9.533 μM against the A549 cell line and 5.244-9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies.

Synthesis, characterization and antibacterial activity of hexasubstituted Coumarin-based Schiff base derivative of cyclophosphazene

This study focuses on synthesis and characterization of hexa-substituted coumarin based Schiff base derivative of cyclotriphosphazene (Compound 3). The antibacterial activity of Compound 3 was evaluated against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa), and Klebsiella pneumoniae (K. pneumoniae) bacterial strains using minimum inhibitory concentration (MIC) and percentage-killing method. Compound 3 exhibited a lower MIC of 300 μg/mL against S. aureus than 500 μg/mL for P. aeruginosa and K. pneumoniae, indicating greater efficacy against Gram-positive bacteria. Percentage-killing data confirmed Compound 3 significant bactericidal activity against S. aureus across concentrations ranging from 100 to 500 μg/mL, comparable to ampicillin. In contrast, its efficacy against Gram-negative strains was lower, suggesting a more selective spectrum of activity. These findings suggest that Compound 3 shows promise as a potential antibacterial agent with preferential activity against Gram-positive bacteria, warranting further investigation into its mechanism of action and therapeutic potential.

In silico studies, synthesis, characterization and in vitro studies of levosulpiride derivatives.

Aim: Breast cancer is the most recurring cancer among females and is being diagnosed as a major cause of death among women.Materials & methods: Levosulpiride Schiff base derivatives were synthesized and analyzed by physical and spectral (FTIR, 1H-NMR, 13C-NMR) analysis. MTT assay against MCF-7 (human breast cancer cell line), scavenging activity and Molecular docking against receptors 1M17, 3PP0, 3IOK and 4KIK along ADME pharmacokinetic studies were performed.Results & conclusion: L1 and L3 synthesized derivatives have revealed better percent cell viability and inhibitory concentration (IC50) with scavenging activity as of the parent compound. L1, L3 and L9 revealed significant docking scores compared with standard drugs. Most of the derivatives showed strong pharmacokinetic profiles while no drug crossed blood-brain barrier. The newly synthesized L1 and L3 levosulpiride-derived compounds have demonstrated promising anticancer properties against breast cancer cells.

Utilization of Schiff base ligands to chelate Ag+ for highly specific and sensitive Hg2+/Ag+ immunoassay

In this study, a planar benzothiazole Schiff base derivative ZX1 was designed and synthesized to selectively precipitate silver ions, in conjunction with the immunoassay detection of Hg2+ ions. The silver chelation process was highly effective in the pH range of 7–10, with a silver ion precipitation ratio of 99.9 %. The coordination behavior of ZX1 with Ag+ was studied using a series of spectroscopic measurements, topography analysis and DFT calculation. The shortest bond distances were 2.251 and 2.254 Å between nitrogen atom of thiazole and Ag+. Weak interactions were analyzed using the interaction region indicator (IRI) method and VMD. The immunoassay was developed through an anti-Hg2+/Ag+ monoclonal antibody, which showed similar sensitivities for Ag+ and Hg2+. The selectivity and anti-interference ability of the Schiff base ligands were tested for some hard metal ions and several anions. With co-existence of interference ion Ag+, Hg2+ was detected in rice matrix solution with 77 %∼123.5 % recovery by addition of ZX1 as the masking reagent and 90.3 %∼115 % for wheat matrix. This research provides a promising immunoassay strategy for simultaneous detection of silver ions and mercury ions in food matrix by utilization of Schiff base ligands. This novel Schiff base ligand was then used as the pre-treatment reagent to remove silver ions within 5 min for detection of Hg2+ or detection of both Ag+ and Hg2+ based on a novel bi-specific heavy metal antibody.

Design, Synthesis, and Study of Novel Memantine Schiff Base Derivatives Against Targeted Enzymes in Alzheimer’s Disease

Introduction: According to WHO, Alzheimer’s disease was estimated at 74.4 million cases in 2023, which will increase by 152.8 million cases in 2050. The therapeutic options available in the market for the treatment of AD are only capable of reducing the symptoms of dementia but not preventing progressive degeneration. Memantine is a non-competitive NMDAR antagonist used for the treatment of patients with moderate-to-severe AD, but it has a high toxicity profile. To counter this, the Memantine Schiff base derivatives were designed as simple and lowtoxicity compounds. Materials and Methods: Molecular docking was performed against the targeted enzymes Acetylcholinesterase and Butyrylcholinesterase using AUTODOCK 1.5.7 software. A series of novel Memantine derivatives of Schiff base were synthesized by condensing Memantine with various aryl aldehydes and screened for their invitro-cholinesterase inhibitory activity towards Acetylcholinesterase (AChE) and Butyrylcholinesterase (BChE) by Ellman’s method. Results and Discussion: Among the designed compounds, compounds LMV and LMC showed maximum binding scores of -10.35 kcal/mol and -10.12 kcal/mol, respectively, than the standard Donepezil (-8.78 kcal/mol) against Acetylcholinesterase. The compounds LMONB and LMDMB produced significant binding scores of -9.31 kcal/mol and -9.11 kcal/mol, respectively, compared to the standard Donepezil (-7.57 kcal/mol) against Butyrylcholinesterase. Also, compounds LMV (30.9 ± 2.13 μM) and LMDMB (13.51 ± 1.12 μM) showed potent inhibitory activity against the AChE and BChE. These compounds possess drug-like characteristics and are also capable of crossing the Blood Brain Barrier (BBB). Conclusion: The studied compounds LMV and LMDMB, being non-toxic, obey Lipinski’s rule of 5 and are potential inhibitors against targeted enzymes, which may be promising clinical candidates for treating Alzheimer’s disease.

A versatile inhibitory approach and molecular mechanism on cancer cells and cholinesterase enzymes: Synthesis, DFT, ADMET and molecular docking of thiadiazole and oxadiazole derivatives

This study presents a multi-routed research design featuring thiadiazole/ oxadiazole based Schiff base derivatives as potential inhibitors, targeting cancer and Alzheimer. Among thiadiazole based Schiff base derivatives, the excellent inhibition was exhibited by compound 1 (IC50 = 20.10 ± 1.1, 22.21 ± 1.03 and 26.23 ± 2.2 µM for HepG2 (liver cancer), MCF-7 (breast cancer) and W138 (lung cancer), respectively) in comparison to the standard Doxorubicin. Oxadiazole based compound 9 was also found with spellbinding efficacy (IC50 =15.20 ± 2.5, 19.13 ± 2.2 and 12.33 ± 3.4 µM for HepG2, MCF-7 and W138, respectively). Both compounds 1(IC50=3.10 ± 0.20 and 3.70 ± 0.10 µM against AChE and BuChE) and 9 (IC50=2.20 ± 0.10 and 2.80 ± 0.50 µM against AChE and BuChE) were also found as excellent anti-Alzheimer agents in comparison to reference donepezil. The outcomes of in vitro biological activity were further studied in silico via molecular docking, DFT and ADMET to elucidate the binding interactions, stability, reactivity and pharmacokinetic profiles of potent compounds.

Synthesis and characterization of some new Schiff base azo disperse dyes based on chromene moiety for simultaneous dyeing and antimicrobial finishing

New azo Schiff base disperse dyes based on a chromene moiety were synthesized by reacting (2-amino-7-hydroxy-4-(4-methoxyphenyl)-4 H-chromene-3 carbonitrile) and(2-amino-4-(3,4-dimethoxyphenyl)-7-hydroxy-4 H-chromene-3-carbonitrile), with vanillin and ninhydrin, producing new chromene Schiff base derivatives, which in turn were coupled with 2-chloro-4-nitroaniline diazonium salt to give new 4 azo disperse dyes (1–4). The structures of the prepared dyes were confirmed using elemental analysis, 1HNMR spectroscopy, mass spectrometry, and IR. The synthesized dyes were applied to polyester and nylon fabrics using different dyeing techniques: high temperature- high pressure, and ultrasonic dyeing methods. The highest K/S values for all investigated dyes were achieved usinga high temperature-high pressure dyeing technique. Also, the color reflectance of all synthesized dyes with different dyeing shades (1%, 2%, and 3%) was obtained. The fastness properties of the dyed samples using the investigated dyes showed good color fastness toward light, washing, rubbing, and perspiration fastness. The presence of a chromene moiety and Schiff base in the investigated dyes promotes a higher antimicrobial activity on nylon and polyester fabrics against all tested bacteria (E. coli gram-negative and Staphylococcus aureus gram-positive) and two fungi, Aspergillus Niger and Candida albicans.

Synthesis, Anti-inflammatory and in silico Studies of few novel 1,2,4-Triazole Derived Schiff Base Compounds

Synthesis, Anti-inflammatory and in silico Studies of few novel 1,2,4-Triazole Derived Schiff Base Compounds

Synthesis of new multi-functionalized Schiff base derivatives based on vanillic acid: Antimicrobial activity, photophysical, DFT calculations and in-silico study

The paper reports the synthesis of novel multi-functional Schiff base derivatives (S1-S7) via Steglich esterification, thoroughly characterized by standard spectroscopic methods (1H NMR, 13C NMR, FT-IR and Mass spectrometry) and elemental analysis technique. Density Functional Theory calculations (including FMOs’, MEP, IR and UV–Visible), photophysical, molecular docking simulations, and in-vitro antimicrobial assays were employed to study the structure and reactivity of synthesized compounds. The study highlights significant antimicrobial activity of certain derivatives, which aligns with computational predictions. UV–Visible study identifies various transitions like π→π*, n→π* occurring in the system aligning with the theoretical absorption spectra. Biological studies reveal that compounds S1, S2 and S5 exhibit significant potency for antimicrobial investigation correlating with the computational study. Further, the calculated HOMO-LUMO band gap for S1-S7 molecules (3.29 eV) suggest their insulating nature. Notably, MEP study shows negative electrostatic potential near nitro group and the positive potential near alkyl groups indicating preferable site for electrophilic and nucleophilic attack, respectively. Moreover, molecular docking was implemented to computationally screen the multi-functionalized Schiff base along with molecular dynamics simulation including MM-PBSA energy calculation in order to discover the reasonable physiological significance ensuring stability of binding interactions of relevant molecules.

Effects of flavonoids on yeast ABC transporters activity

Flavonoids are known to be effective biomodulators of various processes in eukaryotic cells. As these compounds are present in wine and beer raw materials, they can influence the qualitative characteristics of the ethanol content in wine-making and brewing products, including directly through the mechanisms of regulation of gene expression and the activity of ATP-binding cassette (ABC) proteins. The main function of ABC transporters in yeast cells is to transport various substrates, including ethanol. This process ensures the survival of yeast cells under conditions of ethanol stress. It has been found that flavonoids, as well as their Schiff base derivatives, are effective stimulators and inhibitors of mRNA expression and activity of ABC proteins both in logarithmic and stationary phases of growth, which has a direct impact on bioethanol production by yeast.

Furan-Triazine clubbed Schiff base derivatives: Computational insight and empirical precision against A-549 and MDA-MB-468 Carcinoma cells

The purpose of this effort is to generate a range of 1,3,5-triazine substituted furan-2-carbaldehyde Schiff base derivatives (5a-5h) that may be employed as anticancer drugs. The effectiveness of recently synthesised compounds was evaluated in vitro against A-549 lung cancer cell line and MDA-MB-468 breast carcinoma cell line, providing an in-depth evaluation of their possible therapeutic effect on these particular cancer types. Compounds 5e and 5g were found to be the most effective of this series in targeting A-549 lungs cancer cells with IC50 values of 6.33 and 0.31 μM, respectively against the standard drug pictilisib (IC50 1.66 μM), while compounds 5a and 5e were found to be the most promising in targeting MDA-MB-468, with IC50 values of 3.97 and 6.38 μM, respectively, against pictilisib (IC50 3.60 μM). To understand their interaction with the essential proteins involved in the progression of cancer, molecular docking studies were carried out, which gave information about their putative mechanisms of action. Furthermore, molecular dynamics simulations were utilised to analyse the stability and dynamic behaviour of the most active compounds inside the protein binding sites. The study revealed several compounds demonstrating notable anticancer activity, offering encouraging possibilities for their continued development and improvement as novel anticancer medications.

A Captivating Potential of Schiff Bases Derivatives for Antidiabetic Activity.

A double bond between the nitrogen and carbon atoms characterizes a wide class of compounds known as Schiff bases. The flexibility of Schiff bases is formed from several methods and may be combined with alkyl or aryl substituents. The group is a part of organic compounds, either synthetic or natural, and it serves as a precursor and an intermediate in drugs that have therapeutic action. The review focuses on molecular docking and structure-activity relationship (SAR) analysisfor antidiabetic effects of the different non-metal Schiff bases. Many studies have found that Schiff bases are used as linkers in an extensive range of synthesized compounds and other activities. Thus, this current study aims to give the scientific community a thoughtful look at the principal ideas put forward by investigators regarding antidiabetic actions exhibited by certain Schiff-based derivatives, as this review covered many aspects, including docking and SAR analysis. For individuals who intend to create novel antidiabetic compounds with Schiff bases as pharmacophores or physiologically active moieties, it will be an invaluable informational resource.

Novel Schiff base decorated cyclotriphosphazene chemosensors for Fe and Cu ions detection

In this study, new 2-aminobenzothiazole derivative Schiff base decorated cyclotriphosphazene compounds (SBCTP 1 and 2), which are likely to have chemical sensor properties, were designed and synthesized successfully. The compounds were structurally characterized by mass analysis and NMR (1H, 13C and 31P) spectroscopies. Photophysical and chemosensory properties of SBCTP 1 and 2 against some analytes were examined by UV–vis and Fluorescence spectrophotometry. While a significant increase was observed in the UV–vis absorption signals observed at 350 nm with the addition of Fe3+ and Fe2+ ions and a new absorption band was observed at 290 nm with the addition of Cu2+. In addition, according to Job's plot obtained from UV–vis absorption titrations, the complex stoichiometries of SBCTP 1 and 2 with selective analytes were determined as 1:1 (L/M) and 1:2 (L/M), respectively. The selective interaction of donor atoms on SBCTP 1 and 2 with Cu2+, Fe2+ and Fe3+ ions give these compounds chemosensory properties. This study showed that the synthesized Schiff base decorated cyclotriphosphazene compounds (SBCTP 1 and 2) could be new chemosensors with high selective and immediate sensitivity for the detection of iron and copper ions.

Correction: Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Correction: Substituted furan-carboxamide and Schiff base derivatives as potential hypolipidemic compounds: evaluation in Triton WR-1339 hyperlipidemic rat model

Synthesis, in vitro and in silico study of novel 1,3-diphenylurea derived Schiff bases as competitive α-glucosidase inhibitors.

Diabetes mellitus has become a major global health burden because of several related consequences, including heart disease, retinopathy, cataracts, metabolic syndrome, collapsed renal function, and blindness. In the recent study, thirty Schiff base derivatives of 1,3-diphenylurea were synthesized and their anti-diabetic activity was evaluated by targeting α-glucosidase. The compounds exhibited an overwhelming inhibitory potential for α-glucosidase with higher potency ranging from 2.49-37.16 μM. The most effective compound, 5h, showed competitive inhibition of α-glucosidase (K i = 3.96 ± 0.0048 μM) in the kinetic analysis and strong binding interactions with key residues α-glucosidase in docking analysis, indicating its potential for better glycemic control in diabetes patients.