Table 1.
Retrieved from the PDB database are the physiochemical characteristics of 1RV6.
Fig 1.
Chemical structure of 2-phenoxyacetohydrazide.
Scheme 1.
Synthesis of novel phenoxyacetohydrazide derivatives (6e-h).
Table 2.
Retrieved from the PDB database are the physiochemical characteristics of 1EQG.
Table 3.
Retrieved from the PDB database are the physiochemical characteristics of 1CVU.
Fig 2.
Ribbon representation of the crystal structure of vascular endothelial growth factor-A (VEGF-A), retrieved from the Protein Data Bank (PDB ID: 1RV6).
Fig 3.
Visualization of the binding site of vascular endothelial growth factor-A (VEGF-A) (PDB ID: 1RV6).
Fig 4.
Ribbon representation of the crystal structure of cyclooxygenase-1 (COX-1) retrieved from the Protein Data Bank (PDB ID: 1EQG).
Fig 5.
Visualization of the binding site of COX-1 (PDB ID: 1EQG).
Fig 6.
Ribbon representation of the crystal structure of cyclooxygenase-2 (COX-2) retrieved from the Protein Data Bank (PDB ID: 1CVU).
Fig 7.
Visualization of the binding site of COX-2 (PDB ID: 1CVU).
Table 4.
Comprehensive ADMET profile of compound 6e.
Table 5.
Toxicity profile analysis of compound 6e insights from ADMET “SAR” predictions for safer drug development.
Fig 8.
Network diagram illustrating the predicted pharmacological activity profile of the 6e compound.
Fig 9.
Toxicity radar chart representing the predicted toxicity profile of the 6e compound.
Fig 10.
Distribution of dose value of the 6e compound.
Fig 11.
Distribution of molecular weight value of the 6e compound.
Fig 12.
Chemical structural of the compound 6e.
The initial 2D structure was optimized in MOE and converted into a 3D model using Chem3D 16.0.
Fig 13.
A detailed 3D visualization demonstrating the binding interaction of compound 6e (depicted in blue and red) within the active site of the VEGF receptor (PDB ID: 1RV6), represented by green ribbon structures.
This illustration highlights the precise fit of compound 6e into the binding pocket, akin to a key fitting into a lock, emphasizing its potential as a therapeutic agent.
Fig 14.
A detailed 2D schematic representation illustrating the non-covalent interactions that stabilize the VEGF receptor (PDB ID: 1RV6)-compound 6e complex.
This visualization highlights the key hydrogen bonds, hydrophobic interactions, and other stabilizing forces contributing to the assembly’s structural integrity and binding affinity.
Fig 15.
2D interaction of compound 6e (left) and indomethacin drug (right) within the active site of VEGF receptor (PDB ID: 1RV6).
Fig 16.
A captivating 3D visualization showcasing the binding interaction of compound 6e (depicted in red) within the active site of the COX-1 receptor (PDB ID: 1EQG).
Fig 17.
A detailed 2D schematic representation illustrating the non-covalent interactions that stabilize the COX-1 receptor-6e complex.
Fig 18.
2D interaction of compound 6e (left) and indomethacin drug (right) within the active site of cyclooxygenase-1 (COX-1) (PDB ID: 1EQG).
Fig 19.
A striking 3D visualization showcasing the binding interaction of compound 6e (depicted in red) within the active site of the COX-2 receptor (PDB ID: 1CVU).
Fig 20.
A detailed 2D schematic representation illustrating the non-covalent interactions stabilizing the COX-2 receptor (PDB ID: 1CVU)-compound 6e complex.
Fig 21.
2D interaction of compound 6e (left) and indomethacin drug (right) within the active site of cyclooxygenase-2 (COX-2) (PDB ID: 1CVU).
Table 6.
IC50 values (μg/mL) of compounds 6e–6h determined using the human red blood cell (HRBC) membrane stabilization assay (One-way ANOVA, p < 0.0001).
Table 7.
in-vitro anti-inflammatory activity of compound 6e. Data are shown as mean ± (n = 6). (Tukey’s multiple range, post hoc test, p < 0.148).
Fig 22.
Effect of 6e on rVEG F165 induced in vivo CAM. images of the chorioallantoic membrane (CAM) from fertilized chicken eggs after treatment.
Left image (Negative Control): Dense and highly branched neovasculature (black arrows) visible within the yellow demarcation zone, indicating active angiogenesis. Middle image (Positive Control or Standard Treatment): Moderate reduction in vessel density and branching. Right image (Compound 6e-treated group): Marked suppression of neovascularization with sparse, thin, and poorly branched blood vessels, demonstrating significant anti-angiogenic potential.
Fig 23.
Representative histological sections of corneal tissue from experimental groups stained with hematoxylin and eosin: Left image (Negative control): Extensive neovascularization (black arrows) and inflammatory cell infiltration are observed in the stromal layer. Middle image (Indomethacin-treated group): Moderate reduction in neovascular structures (black arrows) and inflammatory cells, with partially restored corneal architecture. Right image (Compound 6e-treated group): Marked improvement in corneal structure with minimal inflammatory infiltration and absence of neovessel, indicating significant anti-inflammatory and anti-angiogenic effects.
Fig 24.
Total vessel length of in vivo CAM.
Each value is expressed as mean ± SD (p < 0.001 versus control, n = 6).
Fig 25.
Effect of 6e on rVEG F165 induced ex-in vivo CAM assay.
Left image (Control + VEGF): Dense and highly branched vasculature (black arrows) radiating from the central embryo, indicating robust VEGF-induced angiogenesis. Middle image (Standard treatment): Moderate reduction in vessel branching and density, consistent with partial anti-angiogenic activity. Right image (Compound 6e-treated group): Marked suppression of new blood vessel formation with sparse and thin vascular branches, indicating significant anti-angiogenic potential of compound 6e.
Fig 26.
Left image (Control + VEGF): Extensive neovessel formation (black arrows) and infiltration of inflammatory cells into the mesodermal layer, indicating strong pro-angiogenic response. Middle image (Standard treatment): Moderate vascular proliferation and inflammation with partial normalization of tissue architecture. Right image (Compound 6e-treated group): Significant reduction in blood vessel formation and absence of inflammatory infiltrate, suggesting strong anti-angiogenic and anti-inflammatory effects of compound 6e.
Fig 27.
Total vessel length of ex-vivo CAM.
Each value is expressed as mean ± SD (p < p < 0.0001versus control, n = 6).
Fig 28.
Angiogenesis modulatory effect of compound 6e on neovascularization (a) Representative photographs of the rat cornea illustrating the inhibition of angiogenesis in alkali-burnt corneas following treatment with compound 6e.
(b) Hematoxylin and eosin (H&E) staining of the cornea reveals improved corneal structure and morphology after treatment with compound 6e. (c) Quantitative analysis showing a reduction in total vessel length in the rat cornea after treatment with compound 6e, demonstrating its efficacy in modulating angiogenesis.
Fig 29.
Photograph of representative rat of each group showing the effect of treatment on paw edema treated with compound 6e.
Fig 30.
H and E staining representative rat changes of each group showing the effect of treatment on paw edema treated with compound 6e.
Fig 31.
Effect of treated with compound 6e on carrageenan-induced paw edema in rat.
The paw swelling ratio is the percent increase of paw volume. Compound 6e significantly inhibited the ratio of paw swelling at 5h after carrageenan injection compared to positive control Indomethacin. Each value is expressed as mean ± SD (p < 0.0001 versus control, n = 3).
Fig 32.
Effect of intraperitoneal administration of compound 6e on myeloperoxidase activity in carrageenan-treated paws.
This figure illustrates the impact of compound 6e, administered intraperitoneally, on myeloperoxidase (MPO) activity in supernatants of homogenates from carrageenan-treated rat paws. MPO activity was assessed 4 hours after carrageenan treatment, highlighting the anti-inflammatory effects of compound 6e Each value is expressed as mean ± SD (p < 0.0001 versus control, n = 6).