2-substituted Derivatives Research Articles

Total Synthesis of (-)-Aspidospermidine via an Enantioselective Palladium-Catalyzed Allylic Substitution Strategy.

A total synthesis of (-)-aspidospermidine via an enantioselective Pd-catalyzed allylic substitution strategy is reported. This represents the first application of a Pd-catalyzed allylic substitution with a 3-substituted indole derivative in the synthesis of Aspidosperma alkaloids. In our synthetic route, the allylic substitution reaction was the stereo defining step. The pentacyclic framework was then constructed in a fully diastereoselective sequence. This culminated in the shortest enantioselective synthesis of aspidospermidine reported to date, in seven linear steps.

Synthesis, structure, and solution chemistry of mixed-ligand oxidovanadium(IV) complexes incorporating ONO donor hydrazone ligands

Four mixed-ligand oxidovanadium(IV) complexes, [VIVO(L1-4)(phen)], 1-4, incorporating tridentate dibasic ONO donor hydrazone ligands (H2L1-4, general abbreviation H2L) derived from the condensation of 2-picolinyl hydrazide with 2-hydroxy acetophenone and its 5-substituted derivatives as primary ligands and 1,10-phenanthroline (phen) as auxiliary ligand have been synthesized in excellent yields. The complexes were characterized by elemental analyses, magnetic susceptibility measurements, and various spectral (e.g. IR, UV–Vis and EPR) studies. The molecular structure of one of the four complexes has been determined by single-crystal X-ray diffractometry. In 1, the hydrazone ligand is meridionally disposed of, coordinating through one enolic-O, one phenolic-O, and one imine-N. The other basal position is occupied by one pyridine-N of the phen moiety. The axial positions are occupied by one oxido-O atom and the other pyridine-N atom of the phen moiety. The complexes are paramagnetic with one unpaired electron (μeff ≈ 1.73 BM), suggesting no interaction with the neighboring molecules and are EPR active. The complexes display two d-d transitions, one near 725 and the other near 840 nm due to d xy → d xz , d yz and d xy → d x 2 − y 2 transitions, respectively. The other d-d transition associated with d xy → d z 2 transition was not observed as it falls in the UV region, which is masked by highly intense intra-ligand transitions. The complexes display one-electron oxidation peaks in the +0.75 to +0.89 V vs. Ag/AgCl region in the CH3CN solution that show a linear relationship with the Hammett parameter (σ) of the substituents in the aryloxy ring.

Anti-inflammatory Activity of 1-Substituted Glyoxal β-Carboline Derivatives

The anti-inflammatory properties of β-carbolines have been widely studied, highlighting their potential in treating inflammatory disorders. This research investigates the anti-inflammatory activity of selected 1-substituted glyoxal β-carboline derivatives, achieved through a one-step conversion of 5-hydroxy-L-tryptophan with activated glyoxal, without forming tetrahydro-β-carboline (THβC) intermediates. These derivatives (4e-g) were synthesized successfully without requiring expensive metal catalysts, prolonged reaction times, or stringent reaction conditions, and yielded moderate amounts. Our findings indicate that all the derivatives significantly inhibit xanthine oxidase (XO) activity, leading to a reduction in reactive oxygen species (ROS) and free radicals. This inhibition disrupts the inflammatory cascade and attenuates the inflammatory response.

HCO-RLF: Hybrid classification optimization using recurrent learning and fuzzy for COVID-19 detection on CT images

COVID-19 infection detection through initial lesion classification provides early diagnosis and prevents breathing difficulties. Detecting the infectious part of the lungs using computerized tomography (CT) images has become an instantaneous detection method. In this article, a Hybrid Classification Optimization (HCO) using Recurrent Leaning and Fuzzy (RLF) is proposed. The neural network classifies infected and non-infected regions using pixel distributions and their variations. This is performed by identifying missing features and training the recurrent network using regional differences. Based on the feature availability, recurrent learning classifies the region through the input dataset and recurrent training correlation. The fuzzy predicts missing features through substituted derivatives obtained between wide ranges of variations. In this process, the maximum fuzzy derivatives for feature substitution are used for infected region prediction. The least fuzzy derivatives are prevented from the training layer to reduce false rates in region classification. This joint process improves the training consistency to leverage the detection and region classification accuracies. The proposed HCO-RLF improves detection and classification accuracy, and precision by 11.96 %, 9.98 %, and 13.42 % for the varying classification rates. Besides, the results are obtained in comparison with the existing DR-MIL, DSAE, and BS-FSA methods discussed later in the article.

Acute toxicity of salicylic acid and its derivatives on the diatom Phaeodactylum tricornutum: Physico-Biochemical and transcriptomic insights

Salicylate pollutants (SAs) poses a serious threat to marine ecosystems as emerging contaminants. However, the toxic effects of SAs on marine phytoplankton, as well as the potential mechanisms and their ecological risks linked with them, are remain largely unknown. In this study, we aimed to evaluate the toxic effects of salicylic acid (SA) and its 5-substituted derivatives (5-sSA) on the marine diatom Phaeodactylum tricornutum, as well as the potential molecular mechanism involved in the toxicity. Physiological assays conducted on P. tricornutum revealed significant changes in photosynthetic pigments, chlorophyll fluorescence parameters, and antioxidant enzyme activities. The results showed that exposure of P. tricornutum to SAs caused a significant decline in chlorophyll contents and damage to the photosystem II (PSII) core resulting in the decline of photosynthesis. Although the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were enhanced, oxidative damage occurred. Transcriptome analysis showed that a large number of differentially expresses genes (DEGs) were significantly enriched in metabolic pathways such as porphyrin metabolism, terpenoid backbone biosynthesis, and carbon fixation in photosynthetic organisms after SA and 5-BrSA treatments. In addition, key genes in transcriptomic metabolic pathways were further analyzed and validated using weighted correlation network analysis (WGCNA) and real-time fluorescence quantitative PCR (qPCR). Considering the above results, SAs mainly inhibit the processes of photosynthesis by repressing the expression of genes involved in secondary metabolite synthesis and photosynthetic carbon sequestration pathways, thus exerting toxic effects on algal cells. The results of the study will provide key data for understanding the ecological risk and toxicity mechanisms of SA pollutants.

Synergic Effects of Ordered Mesoporous Bifunctional Ionic Liquid: A Recyclable Catalyst to Access Chemoselective N-Protected Indoline-2,3-dione Analogous

SBA-15 and organic ionic liquid were incorporated in a post-grafting technique for generating a bifunctional ionic liquid embedded mesoporous SBA-15. The prepared heterogeneous catalyst was employed for the first time to synthesize N-alkylated indoline-2,3-dione at mild conditions to afford excellent yields in a short reaction time. The synthesized DABCOIL@SBA-15 catalyst was meticulously characterized by various techniques, such as FT-IR, solid-state 13C NMR, solid-state 29Si NMR, small-angle X-ray diffraction (XRD), and N2 adsorption–desorption. Further, the morphological behavior of the catalyst was studied by SEM and TEM. The thermal stability and number of active sites were determined by thermogravimetric analysis (TGA). The Hammett equation was used to analyze the synergetic effect of the catalyst and substituent effects on the N-alkylated products of 5-substituted isatin derivatives, which resulted in a negative slope. This negative slope indicates a positive charge in the transition state. Notably, the DABCOIL@SBA-15 catalyst demonstrated its practicality by being reused for seven cycles with consistently high catalytic activity.

Synthesis and antiproliferative activity of 7-substituted amide estradiol derivatives

Synthesis and antiproliferative activity of 7-substituted amide estradiol derivatives

Coumarin-Based Aldo-Keto Reductase Family 1C (AKR1C) 2 and 3 Inhibitors.

A series of 7-substituted coumarin derivatives have been characterized as pan-aldo-keto reductase family 1C (AKR1C) inhibitors. The AKR1C family of enzymes are overexpressed in numerous cancers where they are involved in drug resistance development. 7-hydroxy coumarin ethyl esters and their corresponding amides have high potency for AKR1C3 and AKR1C2 inhibition. Coumarin amide 3 a possessed IC50 values of 50 nM and 90 nM for AKR1C3 and AKR1C2, respectively, and exhibits 'drug-like' metabolic stability and half-life in human and mouse liver microsomes and plasma. Compound 3 a was employed as a chemical tool to determine pan-AKR1C2/3 inhibition effects both as a radiation sensitizer and as a potentiator of chemotherapy cytotoxicity. In contrast to previously reported pan-AKR1C inhibitors, 3 a demonstrated no radiation sensitization effect in a radiation-resistant prostate cancer cell line model. Pan-AKR1C inhibition also did not potentiate the in vitro cytotoxicity of ABT-737, daunorubicin or dexamethasone, in two patient-derived T-cell ALL and pre-B-cell ALL cell lines. In contrast, a highly selective AKR1C3 inhibitor, compound K90, enhanced the cytotoxicity of both ABT-737 and daunorubicin in the T-cell ALL cell line model. Thus, the inhibitory profile required to enhance chemotherapeutic cytotoxicity in leukemia may be AKR1C isoform and drug specific.

Substituent Effect in Salicylaldehyde 2-Furoic Acid Hydrazones: Theoretical and Experimental Insights into DNA/BSA Affinity Modulation, Antimicrobial and Antioxidant Activity

The biological properties of five aroylhydrazones derived from salicylaldehyde and its 5-substituted derivatives with 2-furoic acid hydrazide were thoroughly investigated. NMR analysis confirmed the predominant existence of the aroylhydrazones in the keto-amine form in aqueous solution. Geometries of these compounds were optimized using density functional theory (DFT) calculations with the B3LYP hybrid functional, while ADMET analysis predicted their pharmacokinetic and toxicological properties. Substituent effects on the interactions between the salicyl aroylhydrazones and BSA and DNA were elucidated through experimental and molecular docking studies, revealing the bromo-substituted hydrazone as the most potent binder to both biomolecular targets. Experimental results aligned well with theoretical predictions, indicating that salicyl hydrazones predominantly act as DNA groove binders. Thermodynamic analysis suggested that the hydrazones predominantly interact with BSA through hydrogen bonding and van der Waals forces. Moreover, antioxidant potential assessment using DPPH, ABTS, FRAP, and metal chelating assays demonstrated the potent antioxidant power of nitro and hydroxy-substituted derivatives. Additionally, the antimicrobial properties of hydrazone against Gram-positive and Gram-negative bacteria, as well as fungi, were thoroughly explored, highlighting the nitro derivative as the most prominent candidate with broad-spectrum antimicrobial potential.

Investigation into the Sonodynamic Activity of Three Newly Synthesized Derivatives of Ciprofloxacin.

Sonosensitizers play a crucial role in the efficacy of sonodynamic antitumor therapy (SDT) and sonodynamic antimicrobial chemotherapy (SACT), highlighting the necessity for the development of new compounds with good sonodynamic activity. In this study, three novel 3-substituted ciprofloxacin derivatives (CIPD1, CIPD2, and CIPD3) were designed and synthesized. Their sonodynamic activities were evaluated by assessing the damage to bovine serum albumin (BSA) and Escherichia coli (E. coli). Furthermore, the potential mechanism underlying their sonodynamic damage activities was investigated by detecting reactive oxygen species (ROS) under ultrasound irradiation (US). The results demonstrated that all three derivatives exhibited enhanced sonodynamic damage to BSA and E. coli under US, with CIPD1 and CIPD2 showing superior effectiveness compared to CIP. Both the concentrations of derivatives and the duration of ultrasound irradiation were found to significantly impact their sonodynamic effects. All three CIP derivates could be activated to produce ROS following ultrasound irradiation, primarily consisting of 1O2 and ·OH. The levels of ROS production were positively correlated with their sonodynamic activities, potentially explaining the mechanism underlying their sonodynamic damage activities.

Synthesis of novel 4-substituted isatin Schiff base derivatives as potential autophagy inducers and evaluation of their antitumour activity.

Induction of autophagic death in cancer cells is one of the promising strategies for the development of anti-cancer therapeutics. In the present study, we designed and synthesized a series of isatin Schiff base derivatives containing thioether structures. After discovering the highly active target compound H13 (IC50 = 4.83μM) based on in vitro antiproliferation, we also found it had a high safety against normal cells HEK293 with CC50 of 69.01μM, indicating a sufficient therapeutic window. In addition, to provide reference for subsequent studies, a model was successfully constructed by Sybyl software. Preliminary mechanistic studies suggested that H13-induced apoptosis may be closely related to ROS accumulation and mitochondrial dysfunction. Subsequent studies revealed that H13 inhibited cell proliferation by inducing cellular autophagy mainly through blocking signal of the PI3K/AKT/mTOR pathway. Altogether, these results suggested that H13 was potentially valuable as a lead compound.

Unexplored catalytic potency of a magnetic CoFe2O4/Ni-BDC MOF composite for the one-pot sustainable synthesis of 5-substituted 1-H tetrazoles

Within the domain of materials science and engineering, significant progress has led to the emergence of innovative materials based on magnetic MOFs, positioning them as promising candidates in the field of catalysis. This research aims to elaborate on the development of a finely tailored magnetic MOF composite; Ni-BDC (Nickel benzene-1,4-dicarboxylate) microflakes which was synthesized through a straightforward in-situ solvothermal approach. Extensive investigations into the structural properties of the resultant hybrid composite were carried out using various characterization techniques encompassing X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) analysis, atomic absorption spectroscopy (AAS), energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA) and vibrating sample magnetometry (VSM). The developed material demonstrated remarkable efficiency in expediting the synthesis of a diverse array of pharmaceutically active 5-substituted 1H-tetrazole derivatives through a multicomponent coupling reaction involving substituted aldehydes, malononitrile, and sodium azide as key components. A noteworthy feature of this approach is its adherence to environmentally friendly reaction conditions, thus making it superior in comparison to previously established methodologies. Furthermore, a plausible mechanistic pathway has been proposed to elucidate the impressive performance of the developed catalytic system in the targeted reaction. It is anticipated that the current research will not only contribute to the purposeful designing of advanced magnetic MOF-based architectures but will also play a pivotal role in promoting sustainable practices in industrial processes, addressing pressing environmental and economic concerns.

Exploring the Therapeutic Potential of Benzoxazolone Derivatives on the Circadian Clock: An In Silico and Hypothetical Approach

Objective: Pain conditions exhibit variations linked to circadian rhythms. Circadian rhythms, regulated by clock proteins, impact melatonin levels and immune functions. Melatonin, structurally similar to indomethacin, a non-steroidal anti-inflammatory drug, serves as an alternative in pain-related conditions. Literature suggests a correlation between melatonin-dependent regulation of circadian rhythm and reductions in pain complaints. 2(3<i>H</i>)-Benzoxazolone, known for its anti-inflammatory and analgesic properties, is a promising scaffold for drug design. In this study, pharmacophore analysis focused on benzoxazolone derivatives, evaluating their impact on clock proteins, and providing insights into potential chronotherapeutic implications. Methods: Molecular docking and dynamics simulations were conducted on CLOCK:BMAL1, PER1, PER2, CRY1, and CRY2 clock proteins using benzoxazolone and its 5-substituted derivatives. Molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) calculations were employed to analyze binding free energies. Benzoxazolone derivatives, especially 5-nitro-2-benzoxazolone and 5-fluoro-2-benzoxazolone, exhibited elevated binding affinities on clock proteins compared to melatonin and indomethacin, the reference molecules. The interaction profiles and stability of complexes were maintained throughout the simulations. Results: The results suggest a regulatory impact on CRY proteins, emphasizing their role in circadian rhythm and pain modulation. In addition, the benzoxazolone ring and its derivatives, structurally resembling the core structure of melatonin and indomethacin, demonstrate promising affinities on clock proteins. Conclusion: These findings provide preliminary data and hypothetically propose benzoxazolone derivatives as potential candidates for dual functionality in analgesic activity and circadian rhythm regulation, warranting further in vitro and clinical investigations.

Structural characterization and keto-enol tautomerization of 4-substituted pyrazolone derivatives with DFT approach

The synthesis of two pyrazolone derivative compounds, PYR-I(4-Acetyl-1-(4-chlorophenyl)-3-isopropyl-1H-pyrazol-5(4H)-one) and PYR-II1-(4-Chlorophenyl))-3-isopropyl-5-oxo-4,5-5-dihydro-1H-pyrazole-4-carbaldehyde, their characterization by FT-IR, NMR, UV–Vis and GC-MS techniques, and the evaluation of the keto-enol tautomerization process of the structures along with the DFT approach and spectral data were reported in this paper. Spectral findings indicated that PYR-I was stable at the keto state. The IR spectrum recorded in solid form showed that the PYR-II structure was stable in the enol state, while the NMR spectrum in the solution medium showed that it was stable in the keto state. DFT-based analyses were realized with the B3LYP hybrid functional and the 6–311++G(d,p) basis set. The modelled keto, transition and enol state molecular geometries of structures were optimized in the gas phase and different solvent media and the total energy and dipole moment values were investigated at the specified theoretical level. The possible keto-enol tautomerism mechanism of the structures was evaluated through some thermodynamic parameters such as the difference in free Gibbs energy (ΔG), enthalpy (ΔH), entropy (ΔS), and predictive tautomeric equilibrium constants (Keq), acidity constants (pKa) and percentages of tautomers at 298.15 K and 1 atm pressure. The results of these analyses based on the DFT approach indicated that the keto-enol tautomer equilibrium heavily favours the keto form for PYR-I and the enol form for PYR-II in all cases. Moreover, natural bond orbital (NBO) analysis was performed for the tautomers, and the chemical reactivity profiles of the most stable tautomers were examined with the values of frontier molecular orbital energy and some reactivity descriptors.

Enantio- and Diastereoselective Copper-Catalyzed Borylative Coupling of Styrenes and Azadienes.

Here we disclose a CuB-catalyzed reaction between aurone-derived α,β-unsaturated imines and styrenes to produce 2-substituted benzofuran derivatives bearing both the γ-boryl functionality and α,β-unsymmetric stereogenic centers. The reaction represents the first transition-metal-catalyzed unsymmetric 1,4-Michael additions of azadienes, which would enrich the arsenal of CuB catalysis in organic synthesis. In addition, the synthetically versatile boron-alkylated products can be elaborated by chemical transformations to useful optically active benzofuran heterocycles.

Investigating the potential of 6-substituted 3-formyl chromone derivatives as anti-diabetic agents using in silico methods

In exploring nature's potential in addressing diabetes-related conditions, this study investigates the therapeutic capabilities of 3-formyl chromone derivatives. Utilizing in silico methodologies, we focus on 6-substituted 3-formyl chromone derivatives (1–16) to assess their therapeutic potential in treating diabetes. The research examined the formyl group at the chromone’s C-3 position. ADMET, biological activities, were conducted along with B3LYP calculations using 3 different basis sets. The analogues were analyzed based on their parent structure obtained from PubChem. The HOMO–LUMO gap confirmed the bioactive nature of the derivatives, NBO analysis was performed to understand the charge transfer. PASS prediction revealed that 3-formyl chromone derivatives are potent aldehyde oxidase inhibitors, insulin inhibitors, HIF1A expression inhibitors, and histidine kinase. Molecular docking studies indicated that the compounds had a strong binding affinity with proteins, including CAD, BHK, IDE, HIF-α, p53, COX, and Mpro of SARS-CoV2. 6-isopropyl-3-formyl chromone (4) displayed the highest affinity for IDE, with a binding energy of − 8.5 kcal mol−1. This result outperformed the affinity of the reference standard dapagliflozin (− 7.9 kcal mol−1) as well as two other compounds that target human IDE, namely vitexin (− 8.3 kcal mol−1) and myricetin (− 8.4 kcal mol−1). MD simulations were revealed RMSD value between 0.2 and 0.5 nm, indicating the strength of the protein–ligand complex at the active site.

Design and Synthesis of C₄-Symmetric Axially Chiral β-Aryl Porphyrins and Application for Supporting Ir(III)-Catalyzed Enantioselective C-H Alkylation.

A hitherto unknown class of C4-symmetric Caryl-Cβ (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.

2D QSAR Modelling, Docking, Synthesis and Evaluation of 2-substituted Benzimidazole Derivatives as Anti-breast Cancer Agents

Background: Cancer is a leading cause of death worldwide and is anticipated to reach 28,4 million fresh cases globally by 2040. Despite all the progress made in cancer prevention, diagnosis, and treatment, mortality by cancer is in second place. Objectives: The design of novel 2-substituted benzimidazole modelled by QSAR study. Molecular docking studies on the novel derivatives and synthesis characterization and evaluation of the anticancer activity of the novel derivatives against breast cancer cell line MCF 7. Methods: We designed 10 novel benzimidazole derivatives modeled by 2D QSAR. From the ten compounds by applying insilico tools of ADME properties and toxicity and through molecular docking on Tyrosine Kinase (PDB ID: 2SRC). Compound 2AD showed the highest dock score of -9.5 kcal/mol followed by 2 BD and 2GD (-9.3kcal/mol) Molecular dynamic simulation studies were conducted using CABSflex an online molecular dynamic simulation tool. Six compounds were selected for synthesis. The synthesized compounds were characterized and the invitro pharmacological activity was tested on MCF-7 cell line by MTT assay. Results: The compounds 2AD and 2GD showed good percentage inhibition on MCF-7 cell line withIC50 values of 2.757 µg/ml and 2.875 µg/ml respectively. Conclusion: The novel 2-substituted benzimidazole derivatives are good lead compounds for cancer therapy. Optimization of these compounds will be providing more target-specific anticancer agents.

Structure-Photoreactivity Studies of BODIPY Photocages: Limitations of the Activation Barrier for Optimizing Photoreactions.

BODIPY photocages are photoreactive chromophores that release covalently linked cargo upon absorption of visible light. Here, we used computations of the T1 photoheterolysis barrier to ascertain whether a computational approach could assist in a priori structure design by identifying new structures with higher quantum yields of photorelease. The electronic structure-photoreactivity relationships were elucidated for boron-substituted and core-functionalized 2-substituted BODIPY photocages as well as aryl substitutions at the meso-methyl position. Although there is a clear trend for the 2-substituted derivatives, with donor-substituted derivatives featuring both lower computed barriers and higher experimental quantum yields, no trend in the quantum yield with the computed activation barrier is found for the meso-methyl-substituted or boron-substituted derivatives. The lack of a correlation between the experimental quantum yield with the computed barrier in the latter two substitution cases is attributed to the substituents having larger effects on the rates of competing channels (internal conversion and competitive photoreactions) than on the rate of the photoheterolysis channel. Thus, although in some cases computed photoreaction barriers can aid in identifying structures with higher quantum yields, the ignored impacts of how changing the structure affects the rates of competing photophysical/photochemical channels limit the effectiveness of this single-parameter approach.

Synthesis and anti-inflammatory activity of benzimidazole derivatives; an in vitro, in vivo and in silico approach

Many non-steroidal anti-inflammatory drugs (NSAIDs) concurrently inhibit both COX-1 and COX-2, with a preference for specifically targeting COX-2 due to its significant involvement in various pathologies. In addition to COX enzymes, several other targets, including Aldose reductase, Aldo-ketoreductase family 1-member C2, and Phospholipase A2, have been identified as contributors to inflammation and a myriad of other diseases.In this context, a series of 2-substituted benzimidazole derivatives was synthesized and assessed for their anti-inflammatory potential through both in vitro and in vivo assays. Molecular docking studies were conducted to elucidate the mechanism of action of these compounds against COX enzymes and other therapeutic targets associated with NSAIDs, such as Aldose reductase, AIKRC, and Phospholipase A2.Among the synthesized compounds, B2, B4, B7, and B8 demonstrated IC50 values lower than the standard ibuprofen, as determined by the Luminol-enhanced chemiluminescence assay. Validation of these findings was achieved through an in vivo carrageenan-induced mice paw edema model, confirming a comparable anti-inflammatory effect to diclofenac sodium observed in vitro. Notably, these compounds exhibited significant binding affinity with all therapeutic targets investigated in this study.These results suggest that the newly synthesized derivatives possess noteworthy anti-inflammatory potential, warranting further exploration for the development of novel multi-targeting inhibitors.