Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2

Abstract

To study the involvement of compounds stigmasterol and oleic acid isolated from marine sponge Aurora globostellata and docking against the Human Epidermal Growth Factor Receptor-2 in breast cancer. The comparative molecular docking was performed with the natural compounds from marine sponge and the synthetic drugs used in breast cancer treatment against the target HER2. The molecular docking analysis was done using GLIDE in Schrodinger software package. The ADME properties were calculated using the Qikprop. The observation of the common binding site for all the ligands confirms the binding pocket; where the isolated compound Stigmasterol agrees well with the binding residues and thus can be optimized further to arrive at a molecule that has a high binding affinity and low binding constant. The results of the docking studies carried out on HER2 provide an insight for the compound stigmasterol to have drug like properties than oleic acid. These results are supportive to confirm the marine sponges as a better lead for cancer therapeutics.

Inhibition studies of HBV DNA polymerase using seed extracts of Pongamia pinnata

“…Addition of hydrogen atoms to the protein was performed using CHARMm force field. Energy minimization was performed by using conjugate gradient method with an RMS gradient of 0.01kcal/Å mol on Argus lab [10, 11,12].…”

“…The results of the docking enabled the ranking of the docked conformation of the ligands according to their docking score and hydrogen-binding site. Based on standard antiviral drug, chalcones compound were selected as hits for the target protein [10, 11,12].…”

“…The molecular visualizations of the docked complexes were analyzed using the Argus lab version 4.0.1. [10, 11,12].…”

Cytotoxicity Activity and Druggability Studies of Sigmasterol Isolated from Marine Sponge Dysidea avara Against Oral Epithelial Cancer Cell (KB/C152) and T-Lymphocytic Leukemia Cell Line (Jurkat/ E6-1)

“…In other word, the fraction containing the stigmasterol can only affect cancer cells. Previous studies conducted on stigmasterol extracted from the Aurora globostellata sponge, showed the inhibitory effect on the growth of breast cancer cells (Sugappriya et al, 2017), and observed that, the stigmasterol and its derivatives extracted from Xestospongia sp marine sponge can result in killing 50% of the lymphocyte cancer cells (K562) at 18/3 to 34/3 μg/ml (Cheng et al, 2016). In another study conducted on the cytotoxic properties of the extract containing stigmasterol (more than 25%) from the Spanish and Portuguese marine sponges on the LLC-MK2 healthy cells (epithelial cells from the kidney of the monkey Macaca mulatta), it has been shown that, Tethya ignis (177.5 μg/ml), Tethya rubra (172.5 μg/ml), Dysidea avar (144.2 μg/ml), and Mycale angulosa sponges (302.71 μg/ml) can exhibit lethal effects (Paula et al, 2015).…”

Isolation, identification, and cytotoxicity evaluation of phytochemicals from chloroform extract of Spathodea campanulata

“…Numerous studies have reported the cytotoxic activity of isolated compounds against different human cancer cell lines, viz., stigmasta-5, 22-dien-3-ol, octadecenamide, and umbelliferone through various mechanisms and pathways. The anticancer activity of stigmasterol against Ehrlich ascites carcinoma [21], breast cancer cells [30], liver cancer cells [31], and Hela cells [32] were reported in the literature. The anticancer activity of umbelliferone against HepG2 hepatocellular carcinoma cells via the induction of apoptosis and cell cycle [33] and human renal cell carcinoma [34] were reported.…”