Position Of Ring Research Articles

Synthesis of Novel 3,4-Dihydropyrimidine Derivatives, Cytotoxic Activity Evaluation, Apoptosis, Molecular Docking Studies, and MD Simulations.

In this study, twelve 3,4-dihydropyrimidines derivatives were synthesized through Biginelli multi-component reaction. The efficacy of these compounds against MCF-7, A549, and HeLa cells was evaluated using the MTT method. The results showed that designed derivatives were more effective against A549 cancer cells than MCF-7 and HeLa cells. Compound 5l (bearing 4-Cl-phenyl at C4 of 3, 4-dihydropyrimidin-2(1H)-one ring) was the most potent analogue (A549: 18.65±1.87 μM, HeLa: 26.59±2.71 μM, MCF-7: 31.82±2.64 μM). The presence of an electron-withdrawing group with optimum lipophilicity at the C4 position of the phenyl ring increased the cytotoxic effect. The flow cytometry findings indicated that compound 5l induced apoptosis in A549 cancer cells in a dose-dependent manner. Eg5 and AKT1 were selected as molecular modeling target by applying pharmacology network analyses. The molecular docking results indicated that both enantiomers of compound 5l had significant interactions with key residues in both Eg5 (Gly117 and Glu116) and AKT1 (Ala123 and Glu121) active sites. However, MD simulation revealed that the R enantiomer had a more stable complex and a higher binding affinity to the Eg5 enzyme active site than the S-enantiomer. The affinity of 5l (R enantiomer) to Eg5 was predicted more than AKT1.

Synthesis of rhodamine B amine derivatives with improved light resistance and its application in thermochromic materials

Rhodamine B (RhB) is a widely utilized xanthene dye known for its strong fluorescence, high quantum yield, bright color, and versatility in various applications. However, RhB type dyes face significant limitations due to their susceptibility to photodegradation. Herein, four RhB amine derivatives (RhB-1, RhB-2, RhB-3, and RhB-4) were synthesized to improve the light resistance through functionalization of the 4′ position of the carboxyphenyl ring with acrylamide, butylamine, octylamine, and cyclohexanamine, respectively. The mechanism of improving light resistance was analyzed. The results show that the derivatives demonstrated significantly enhanced light resistance compared to RhB, with the ability to form supramolecular structures including dimers and aggregates that protect against UV degradation. Light resistance for RhB-1 was significantly improved with increasing concentration as the photodegradation efficacy drops from 84.8 % (1.5 × 10−5 mol/L) to 10 % (2.0 × 10−4 mol/L), due to the dominant changes from monomers to J-dimers to H-aggregates. When incorporated into three-component thermochromic systems, the derivatives not only improved the light resistance with double duration of UV irradiation but also expanded the range of color change temperatures. This work advances the development of RhB derivatives with superior optical properties and durability, enhancing its applicability in environments requiring prolonged exposure to light.

Dual pH-responsive polypeptide nanoprobes for lysosomes enhanced bioimaging and tumor photothermal therapy under 1064 nm irradiation

Cancer cell precise fluorescence imaging and following tumor photothermal therapy have garnered ongoing interest. Lysosomes in cancer cells in a typical acidic environment can be used for smart bioimaging, and intelligent NIR-II fluorescence probes are attractive for tumor phototheranostics. Here, we successfully synthesized a pH-responsive NIR-II fluorescent dye FPZ and the introduction of N-methylpiperazine moiety at the ring position in the dye-endowed FPZ with fluorescence enhancement under acidic response. A pH-sensitive amphiphilic polypeptide was selected as the carrier to prepare FPZ-PN nanoparticles, which could be disassembled under acidic stimulation for efficient drug delivery and enrichment, and its fluorescence was significantly restored and enhanced (fluorescence enhancement of about 4.2 times) because of the blockage of the photoinduced electron transfer process, which allowed for efficient NIR-II fluorescence imaging, especially the lysosomes in cancer cells. In addition, the nanoparticles exhibited great photostability and a significant photothermal effect, with a photothermal conversion efficiency reaching as high as 69.96 % when subjected to a 1064 nm laser irradiation, which can effectively kill tumor cells. Thus, this work provides a new effective strategy for designing smart-responsive nanomedicine systems for precise localization and tumor elimination.

Synthetic Strategies and Applications of Fluorine‐Containing Bridged Bicyclic Compounds

AbstractBridged bicyclic compounds (BBCs) have recently emerged as effective 3D‐isosteres of planar aryl and heteroaryl rings. Current synthetic endeavours are devoted to accessing these complex structures bearing functionalities in different positions of the aliphatic rings. Of particular interest is the incorporation of F‐containing motifs, since it allows the generation of isosteric units with improved physicochemical properties, including lipophilicity, water solubility, or oxidative resistance.

Mono-/multi-fluorination of 1,8-naphthalimides for developing AIE/AIEE fluorophores with tuning emission wavelength

Aggregation-induced emission/aggregation-induced emission enhancement (AIE/AIEE) luminogens provides amount of highly emissive materials in density states for versatile applications. Most of the AIE/AIEEgens were designed with the multiply rotation unit, in which the additional rotation units not only extend the molecular structure but also suffer from low atom economy. Herein, a fluorination strategy was introduced to construct ten AIE/AIEEgens with 1∼3 fluorine (F) atoms at different position of phenyl ring at previous developed AIEgen, 4-phenyl-1,8-naphthalimide, which can output tuning emissive wavelength and high quantum yields in both aqueous solutions and solids. In these compounds, five AIEgens with ortho-F atom and five AIEEgens without ortho-F atom were obtained. All compounds show bright blue emissions centered at 430–485 nm in aqueous solutions and wide emissions covering visible region in solid states. We calculated the ratio of quantum yields between their aqueous solution and THF solution (Φwater/ΦTHF). The AIE luminogens show the higher ratios between 10.19 and 24.89 and the AIEEgens show the lower ratios between 1.89 and 6.40. This strategy based on changing the substituent positions of F atoms provides an efficient and convenient method for construction of novel AIE-active materials with variable photophysical properties in density states.

A Facile and Regioselective Synthesis of 2‐Formamidothiazoles via the C−H Formamidation of Thiazole N‐oxides with Isocyanides

A facile, microwave‐promoted, regioselective C−H formamidation of thiazole N‐oxides with isocyanides in the presence of TBDPSCl was developed. Various 2‐(N‐substituted formamido)thiazoles were obtained in moderate to high yields. In the case of the C2‐substituted thiazole N‐oxides, the C‐H formamidation took place selectively at the C4 position of the thiazole ring. This transformation is also applicable to some other N‐containing heterocyclic derivatives such as pyridine, quinoline, and pyridazine N‐oxides and has advantages such as broad substrate tolerance, high regioselectivity, and mild reaction conditions.

Quercetin analogues of kojic acid as strong antioxidant derivatives: Theoretical insights

Kojic acid is a natural product produced by many fungal species and has a wide range of applications. The chelating and antioxidant capacity are associated with their chemical and biological properties. In this study, some molecular modifications were proposed and substituted and hydroxylated phenyl moieties were introduced in the basic structure of kojic acid. The antioxidant capacities were calculated by DFT/B3LYP/6-311++G(2d,2p). Different antioxidant mechanisms were considered such as frontier molecular orbitals (HOMO, LUMO, and GAP), electron (IP, SET, and SPLET), or hydrogen transfers (BDEOH and HAT) on gas phase and PCM methods. The phenyl increases the antioxidant capacity, especially when an electron donating group (EDG) is found at the para position of the phenyl ring when compared to electron withdrawing groups (EWGs), for all studied mechanisms. The chemical stability agrees with spin density contributions for their cationic free radicals and semiquinones. A structural similarity between hydroxylated derivatives of kojic acid and quercetin was observed on gas phase and water. The lower BDEOH values ​​at the phenol positions are more important for the antioxidant capacity than at the enol position. Phenolic semiquinones are more stables than enolic ones. The chemical stability depends on the number of resonance structures and the positions where the unpaired electron can be found with the highest contributions. In conclusion, phenyl substitution is a valuable molecular modification for the increase on antioxidant capacity of kojic acid. Quercetin analogues of kojic acid were proposed as strong antioxidant derivatives.

Dibenzoxanthene-β-lactam hybrids as potential antioxidant and anticancer agents: Synthesis, biological evaluation, and docking study

In this study, we designed and synthesized a series of β-lactam compounds bearing 14-phenyl-14H-dibenzo[a,j]xanthene moiety attached to the N-1 position of the β-lactam ring through a [2 + 2] cycloaddition process. All the synthesized compounds have been characterized by elemental analysis, Fourier-transform infrared (FT-IR) and nuclear magnetic resonance (1H NMR and 13C NMR) spectral analysis. These derivatives were evaluated for their anticancer and antioxidant activities. The in vitro anticancer activity of new compounds was examined against MCF-7 (breast cancer), HepG2 (liver hepatocellular carcinoma), and TC-1 (mouse lung epithelial) cell lines by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Notably, compounds 4c, 4e and 4 g demonstrated significant anticancer activity against TC-1 cell line. Additionally, compounds 4c, 4f and 4 g exhibited promising levels of efficacy against the MCF-7 cell line. The diphenylpicrylhydrazyl (DPPH) radical scavenging assay indicated that 4h and 4i are more potent antioxidant agents than the Vitamin C, while 4a, 4b, 4c, and 4j exhibited moderate antioxidant capabilities. Furthermore, the docking simulations are consistent with the biological assay results, indicating that the hybrids may bind to protein targets through hydrogen bonding and other nonvalent interactions.

Multicomponent Synthesis of C(8)-Substituted Purine Building Blocks of Peptide Nucleic Acids from Prebiotic Compounds.

We have explored the reaction of a three-components mixture of aminomalononitrile, urea and α-amino acid methyl esters for the multicomponent synthesis substituted purines resembling PNA's building blocks. 2,6-diamino-purines, 6-amino-3,9-dihydro-2H-purin-2-one (iso-guanines), and 3,9-dihydro-6H-purin-6-one derivatives, selectively decorated at C(8)-position of the purine ring with different amino acid residues, were obtained from acceptable to good yields. The regio-selectivity of the transformation was controlled by the use of urea in the ternary mixture and by the annulation agent involved in the ring-closure of amino-imidazole carbonitrile intermediates. Solvent free conditions, microwave irradiation and simple one-carbon containing reagents further satisfied the major requirement of atom economy and sustainable chemistry. Due to the prebiotic nature of the three-components mixture and of annulation agents, it also embodies the possibility for the synthesis of novel PNAs bearing purine nucleobases decorated at C(8)-position of the imidazole ring as alternative RNA analogues in molecular evolution.

Synthesis of Alkyl/Aryloxymethyl Derivatives of 1,2,4-Triazole-3-Carboxamides and Their Biological Activities.

Ribavirin and its analogues exhibit an in vitro antiproliferative effect in cancer cells. In this work, we studied the biological activities of a number of alkyl/aryloxymethyl derivatives of ribavirin's aglycon-1,2,4-triazole-3-carboxamide. Alkyl/arylxymethyl derivatives of 1,2,4-triazole-3-carboxamide with substitutions at the fifth or first position of the triazole ring, were synthesized and their antiproliferative and antimicrobial effects were assessed. For both series, the presence of an antiproliferative effect was investigated, and 1-alkyl/aryloxymethyl derivatives were shown an antimicrobial potential against a Gram-positive bacteria Micrococcus luteus and Gram-negative bacterium Pseudomonas aeruginosa. The obtained results showed that the n-decyloxymethyl derivatives induced leukemia cell death at low micromolar concentrations. We confirmed that n-decyloxymethyl derivatives of ribavirin inhibited the cell cycle progression and induced an accumulation of leukemia cells in the subG1-phase. The molecular docking results suggest that alkyl/aryloxymethyl derivatives may act by inhibiting translation initiation, due to interference with eIF4E assembly. The outcome results revealed that active derivatives (1- or 5-n-decyloxymethyl-1,2,4-triazole-3-carboxamides) can be considered as a lead compound for anticancer treatments.

Abruptly autofocused electron beam generation through electron-plasmon interactions.

Electron Airy beams and electron vortex beams are commonly generated using phase masks that imprint a transverse modulation on the particle wave function. Plasmons sustained by nanostructured conductors facilitate substantial interactions with free electrons, enabling considerable transverse modulation of the electron wave function. Consequently, electron Airy and vortex beams can also be produced through interactions between electrons and structured plasmonic fields. Here we illustrate the generation mechanism of the electron ring Airy vortex beams by allowing electrons to traverse an Airy plasmon field with phase singularities and calculate the excitation intensity probability. Subsequently, we numerically investigate the autofocus behavior of the generated Airy vortex beams. Our findings indicate that electrons in the ℓ = 1 channel exhibit the highest excitation probability and produce optimized autofocused ring-shaped Airy vortex beams in our proposed scheme. Furthermore, the number of exchanging plasmons does not significantly influence the position of the primary Airy ring in the initial plane, yet it markedly affects the focal distance and spot size in the focal planes. Our study supports the utilization of chiral plasmons sustained by externally illuminated thin films as a method for generating autofocused chiral electrons, resulting in remarkably large diffracted beam fractions in attainable conditions.

Light rings and shadows of static black holes in effective quantum gravity

Recently, two types of static black hole models that retain general covariance have been proposed within the Hamiltonian constraint approach to effective quantum gravity (EQG). We have studied the light rings and shadows of these black holes using the topological method and the backward ray-tracing method, respectively. We demonstrate that these light rings in both types of static black holes are standard and unstable according to the classification of light rings. Subsequently, we checked the position of the light rings using the photon trajectory equation. We found that although the quantum parameters do not affect the light rings of these two types of black holes, they do reduce the size of the first type of static black hole in EQG, making it smaller. However, for the second type of static black hole in EQG, we cannot distinguish it from a Schwarzschild black hole based on the shadow alone. Fortunately, the quantum parameters shrink the lensing rings of both types of black holes in EQG, causing the black hole shadow to occupy a larger proportion within the ring. This can serve as a basis for distinguishing whether the black hole is in EQG or general relativity (GR).

Design of novel copper(I) metallomesogens with benzoylthiourea ligands having peripherally connected cyano or fluoro groups

A new set of liquid crystals based on copper(I) complexes with a cyano or fluoro group attached at the para position of an aromatic ring in a benzoyl thiourea ligand was prepared and studied for their liquid crystalline properties. Incorporating electron-withdrawing fluoro or cyano groups into the structural matrix can enhance their thermal stability, phase transition temperatures, and optical properties. The prepared Cu(Ln)2X compounds, where X = Cl, Br, or I, and 4-(dodecyloxy)-N-((4-fluorophenyl)carbamothioyl)benzamide (L1), N-((4-cyanophenyl)carbamothioyl)-4-(dodecyloxy)benzamide (L2), N-((4-fluorophenyl)carbamothioyl)-3,4-bis(octyloxy)benzamide (L3), and N-((4-cyanophenyl)carbamothioyl)-3,4-bis(octyloxy)benzamide (L4) displayed a SmA mesophase depending on the type of the attached terminal group (F or CN), number of alkoxy chains (one or two) and the nature of the halide ion coordinated to the metal center (Cl, Br or I). The structures of the compounds were characterized by 1H and 13C NMR, ESI-MS and IR studies, and their mesomorphic properties were investigated via a combination of polarising optical microscopy (POM), differential scanning calorimetry (DSC), and powder X-ray diffraction studies. These compounds were stable throughout the temperature range of the mesophases. This study further reiterates the consequential effect of incorporating cyano or fluoro groups on the mesomorphic and the size of the halide ions of the studied compounds.

Synthesis and pharmacological evaluation of nature-inspired phenacyl glycosides

Phenylethanoid glycosides are a well-studied class of bioactive compounds found throughout the plant kingdom. In contrast, research on the synthesis and pharmacological activity of phenacyl glycosides, a specific subgroup of phenylethanoid glycosides with a ketone functionality at the alpha position of the phenol ring, has been limited. In this study, we report the synthesis, cytotoxic, antiviral, and anti-inflammatory evaluation of a series of 18 4′-hydroxyphenacyl glycosides. These compounds consist of six different sugar residues (β-d-glucose, β-d-galactose, α-l-arabinose, β-d-xylose, α-l-rhamnose, and β-d-glucuronic acid) and display three distinct methoxylation patterns at the phenacyl ring, similar to the substitution motifs of anthocyanins. We obtained the target phenacyl glycosides in high yield and stereoselectivity through the coupling of benzoyl-protected trichloroacetimidate glycosyl donors and corresponding acetophenones. Our work represents the first total synthesis of the natural products 4′-hydroxyphenacyl-β-d-glucopyranoside (1) and 4′-hydroxy-3′-methoxyphenacyl-β-d-glucopyranoside (2). None of the phenacyl glycosides showed cytotoxicity against the tested cell lines. Notably, several of the synthesized compounds exhibited antiviral activity, with natural product 2 being the most active against herpes simplex virus type 1, while phenacyl arabinoside 9 and natural product 2 were the most active against human coronavirus OC43. Natural product 2 significantly inhibited the production of interleukin-6 in lipopolysaccharide-stimulated microglia cells. Overall, our findings highlight the importance of the sugar residue and phenacyl ring substitution pattern in modulating the antiviral activity of phenacyl glycosides. Natural product 2 and phenacyl arabinoside 9 emerge as promising leads for the development of antiviral agents.

Mechanistic Understanding of the Underlying Energy Storage Mechanism of α-MnO2-based Pseudo-Supercapacitors.

Manganese dioxide (α-MnO2) has attracted significant research interest in supercapacitors recently. However, the reaction mechanism of α-MnO2 in supercapacitors remains unclear. Therefore, a nano-supercapacitor using Environmental transmission electron microscopy (ETEM) is conducted and investigated the reaction mechanism of α-MnO2 based on three ionic liquids (ILs). It found that in the aprotic ionic liquid (AIL) 1-ethyl-3-methylimidazolium trifluoromethanesulfonate (EMIMOTF), α-MnO2 nanowires (NWs) undergo an oxidation reaction due to the presence of an active proton at the second position (H2) of the imidazole ring. As a result, α-MnO2 NWs undergo a phase transition and transform into Mn3O4, exhibiting pseudo-capacitive properties. Furthermore, characterization of the macroscopic α-MnO2 electrodes after cycling reveals that after the initial charging cycles, the dominant energy storage mechanism of the supercapacitor transitions from pseudo-capacitance to a dual-layer capacitance formed by the combination of Mn3O4 and unreacted α-MnO2. Simultaneously, due to the coexistence of these two energy storage mechanisms, the specific capacitance of the supercapacitor in EMIMOTF electrolyte reaches up to 80 F g-1, and the cycle number reaches as high as 1000 cycles. The results are expected to provide insights into the selection of electrolytes in supercapacitors and offer a fundamental understanding of the internal reaction mechanisms in capacitors.

Synthesis, spectroscopy and biological investigation via DFT, ADMET and molecular docking of Thiadiazole/Oxadiazole based bis-Schiff bases: A potential towards diabetes and microbes

A novel series of varied substituted thiadiazole/oxadiazole based bis-Schiff base derivatives (1–10) was synthesized and characterized using NMR (13CNMR and 1HNMR) and HREI-mass spectrometry. To determine their anti-diabetic potential, these analogues were examined against α-amylase and α-glucosidase. These compounds demonstrated varied inhibitory range between IC50 = 1.10 ± 0.50 to 21.40 ± 0.20 µM (α-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (α-glucosidase), when contrasted with Acarbose, a well-known marketed drug (IC50 = 3.16 ± 0.22 &4.8 ± 0.21 µM for α-amylase and α-glucosidase respectively). Analog-9 having tri-fluoromethyl group at para position of benzene ring emerged as lead candidate among these synthesized compounds. The effective activity of compound-9 may be due to involvement of fluoro atoms interacting via hydrogen-bonding with the selected sites of diabetic enzymes, α-amylase and α-glucosidase. Furthermore, for exploration of binding interactions of potent drugs and reactivity of potent analogues, molecular docking as well as DFT was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.

Insights into the role of potent thiadiazole based Schiff base derivatives in targeting type-II diabetes: A combine in-vitro and in-silico approaches

A novel series of varied substituted thiadiazole based Schiff base analogues (1–21) were designed and characterized using NMR (13C, 1H) and HREI-mass spectrometry, and secerned against the enzymes responsible for hyperglycemia i-e α-amylase and α-glucosidase. Newly designed analogues demonstrated distinct inhibitory activities having IC50= 1.10 ± 0.50 to 21.40 ± 0.20 µM (for alpha-amylase) and 2.50 ± 0.05 to 21.40 ± 0.10 µM (for alpha-glucosidase) in contrast to acarbose a well-known marketed drug (IC50 = 3.16 ± 0.22 & 4.8 ± 0.21 µM for α-amylase and α-glucosidase, respectively). Compound (20) with tri-fluoromethyl at para position of aromatic ring revealed as lead candidate among the members of synthesized series, having effective inhibitory activity against enzymes α-amylase and α-glucosidase. The excellent activity of compound (20) might be due to involvement of fluoro atom interacting via H-bonding with the active sites of enzymes α-amylase and α-glucosidase being targeted. Furthermore, for exploration of binding interactions of potent drugs, molecular docking was performed. For investigation of drug likeness and toxicity, ADME analysis was also conducted.

Investigation of the Fluorination Step in the Biosynthesis of Nucleocidin

Natural products (NPs) are secondary metabolite compounds produced by living organisms like bacteria and fungi. NPs and their derivatives commonly have biological activity and contribute to the development of pharmaceuticals, particularly antibiotics. NPs are encoded by biosynthetic gene clusters, which are sets of genes that when collectively expressed, lead to the production of these compounds. Nucleocidin is an NP derived from adenosine and is produced by Streptomyces species. Its 4’-fluoro and 5’-O-sulfamoyl groups make nucleocidin of particular interest, as it is one of the few natural products known to contain fluorine. Additionally, the incorporation of fluorine at the 4’ position of the adenosine ring requires novel fluorine chemistry, since previously characterized fluorinases have only been known to substitute fluorine at the 5’ position. Previously, three candidate fluorinase genes from the nucleocidin biosynthetic gene cluster, ORF2, 3, and -3, were identified using a genome mining approach and cloned for gene expression in E. coli. In-vitro assays were performed with the purified fluorinase enzymes, but the results were inconclusive regarding enzymatic characterization and association with the fluorination of nucleocidin. This project builds on previous experimentation to prove the fluorination activity of these enzymes through an in-vivo system. The three candidate fluorinase genes, along with a glucosyltransferase essential to the fluorination process, were cloned into a duet-vector system and expressed in a medium supplemented with fluorine. The extracted compounds were analyzed using UPLC-MS, but the results were inconclusive. Further steps will include screening media conditions for nucleocidin production in a heterologous system, and optimizing the in-vivo expression of the potential fluorinase genes. Ultimately, further characterization will be necessary to reveal the specific role each of these candidate fluorinase enzymes plays in the biosynthesis of nucleocidin. Future exploration into the fluorination of nucleocidin offers novel insights into increasing the production efficiency of nucleocidin and its derivatives for pharmaceutical development, along with providing potential avenues for bio-catalytically introducing fluorine into new pharmaceuticals.

Magnetometry for the Muon g-2 Experiment

The Muon g-2 Experiment at Fermilab aims to measure the muon anomalous magnetic moment with a precision of 140 parts per billion (ppb). The collaboration has published the latest measurement based on the first three Runs (collected from 2018 to 2020) in August 2023 with a precision of 200 ppb. The experiment accumulated three more years of data, from 2020 to 2023, which are currently being analyzed. This additional statistic is sufficient to achieve and possibly exceed the goal of 100 ppb of final statistical uncertainty. As the statistical error reduces, increasing attention is dedicated to studying systematic uncertainties. Among them, one source is a magnetic transient generated by the fast kickers. To center the muon orbit into its final position in the storage ring, three kickers emit a 120 ns magnetic pulse of ∼240 G, right after injection. This, however, induces eddy currents in the kicker aluminum structure that last for several microseconds. To measure the 10 mG magnetic perturbations generated by the eddy currents, the INFN team developed a laser magnetometer based on the Faraday effect. This article describes the technical principles, operations, and data analysis of this very sensitive device.

Computational assessment of the reactivity and anticancer activity of 1,2,3-triazole-thiazolidinones derivatives: An approach combining DFT calculations, molecular dynamics simulations, molecular docking, and ADMET

Cancer is a global health burden with escalating incidence and mortality rates, necessitating the exploration of novel therapeutic strategies. 1,2,3-Triazoles, recognized for their diverse biological activities, have emerged as attractive candidates in drug discovery targeting key proteins associated with various cancers. This study presents the synthesis of a library of 1,2,3-triazole hybrids incorporating thiazolidinone and isoxazoline moieties. The antitumor potential of these compounds was evaluated using both in-silico and in-vitro assays. Structure-activity relationship (SAR) analysis revealed that strategic substitution of the para position of the phenyl ring, particularly with a nitro (NO2) group, is promising to enhance cytotoxic activity. The binding potential of the synthesized compounds with the XIAP BIR2 domain, the specific receptor of caspase-3/7 activators, was explored through molecular docking. The stability of the protein-compound complexes procured from the docking was assessed through molecular dynamics (MD) simulation. The docking study demonstrated that the synthesized compounds had the potential to bind to the target protein. Among the compounds and their stereoisomers, compounds (R)-6d and (S)-6e exhibited a better binding potential to the protein. The MD simulation study revealed that the protein-(R)-6d complex was relatively stable.