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Purpose: In recent year’s anti-angiogenesis agents have been recognized as effective drugs for the treatment of solid tumors, this prompted us to conduct the present study. Methods: The anti-angiogenic activity of dimeric form of embelin (vilangin) was evaluated using endothelial cell (in vitro) and chorioallantoic membrane (CAM) egg yolk angiogenesis model (in vivo) and in addition the docking behaviour of human nitric oxide synthases (NOS) with four different ligands was evaluated along with their putative binding sites using Discovery Studio Version 3.1 (in silico) compared with the parent compound (embelin). Results: Vilangin exhibits 50% cytotoxic at 92 ± 1 µg/ml concentration level with reference to ECV 304 endothelial cells. Both vilangin and embelin, showed inhibitory effects on wound healing, single cell migration, nitric oxide production, and endothelial ring formation at 0.1 and 1.0 μg/ml concentration level. Similarly, CAM assay also showed inhibitory effect of vilangin and embelin with respect their reduction in length, size and junctions of blood capillaries compared to untreated egg yolk. Docking studies and binding free energy calculations revealed that vilangin has maximum interaction energy (-74.6 kcal/mol) as compared to the other investigated ligands. Conclusion: The results suggest that both vilangin and embelin attenuates angiogenesis in similar manner.

A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure–activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.

Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.

In the present study, we aimed to dock 17 different ligands of curcumin analogues with that of human neutrophil elastase. Molecular descriptors analysis using Molinspiration online tool was carried out including investigation on human neutrophil elastase putative binding sites using Discovery Studio. The molecular physicochemical analysis revealed that all of the curcumin analogues complied well with the five rules of thumb. With regard to bioactivity score, compound 17 has exhibited least score towards nuclear receptor ligand (0.05) and enzyme inhibitor (0.10) compared to all other ligands. Compounds 2, 4 and 13 exhibited the maximum interaction energy (-40 kcal/mol). Interestingly, seven compounds namely 3, 11-14, 16 and 17 interacted well with Arg147 amino acid residue. The present study outcomes, therefore, might provide new insight in understanding these 17 curcumin analogues as potential candidates for human neutrophil elastase inhibitory agents.