Diterpenoids profile of the marine sponge Chelonaplysilla erecta and candidacy as potential antitumor drugs investigated by molecular docking and pharmacokinetic studies

Abstract

The Chelonaplysilla genus possesses a numerous bioactive diterpenes with antiinflammatory and cytotoxic effects. The current study aimed to assess the chemical composition of C. erecta crude extract (CECE) based on its metabolomic profile that has been integrated with neural network-based virtual screening and molecular docking using liquid chromatography with high resolution mass spectrometry (LCHR-MS). In addition to the estimation of the antitumor activity of the same extract via anti-interleukin-17A (IL-17) action, along with its formulated spanlastics preparation. The CECE markedly displayed growth inhibition for HepG-2 cells at IC 50 value 16.5 ± 0.8 μg/mL, whereas the spanlastic formulation revealed more eminent antitumor effect against Caco-2 cells (IC 50 = 2.8 ± 0.03 μg/mL). Among the dereplicated compounds, macfarlandin F ( 16) and pourewanone ( 25) demonstrated the highest potential with co-crystallized ligand 63O within the active site of IL-17A in molecular docking studies. These findings rationalized the antitumor mechanism of marine organism for future chemotherapeutic applications. Experimental Sponge materialThe marine sponge Chelonaplysilla erecta was collected by Prof. D. Hajjar and A. A. Makki, from the Red Sea, Jeddah side. The sponge possessed an upright growing skeleton with long and thick spongin fibres. Characteristically, the dendritic fibres anastomose frequently with each other in agreement with previous literature (Tsurnamal 2013). The specimens were washed then with 1% phosphate buffered saline (PBS), immediately on the boat. The specimens with their label were wrapped in aluminium foil and placed on ice, then stored at -80 °C until further processing. The specimen's surface peel was removed and immersed in xylene for 24 hours. DPX (Dibutyl Phthalate Polystyrene Xylene) was used to mount a permanent slide of the peel. Under a stereo microscope, a single fibre with its base and branches intact was extracted from the sponge for species identification. Sponge samples were identified by Prof. Dr. El-Sayd Abed El-

Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway

“…Molecular Operating Environment (MOE® 2014.0901) software was used to evaluate and examine possible interactions of test molecules ( VIc , VIf , VIg , VIi , and VIk ) within crystal structure of 3 target proteins: Epidermal growth factor receptor (EGFR; PDB ID: 1M17), BRAF V600E kinase (PDB ID: 4MNF) and cyclin-dependent kinase (CDK2; PDB ID: 1PYE) obtained from RSCB protein data bank 34 and results in the form of docking score (S; kcal/mol), docking accuracy expressed as root-mean square deviation (RMSD; Å) and binding interactions with various amino acid residues lining active site (as listed in Table S1 ). Preparation of structural formulas of test molecules and structure of target proteins were performed as reported elsewhere 35 . Validation of prepared protein structures was done via re-docking of co-crystallised ligands with their protein crystal-structure obtained from RSCB protein data bank and their docking score and RMSD values were within acceptable range for running docking simulations within target proteins (as listed in Table S1 ).…”

“…Validation of prepared protein structures was done via re-docking of co-crystallised ligands with their protein crystal-structure obtained from RSCB protein data bank and their docking score and RMSD values were within acceptable range for running docking simulations within target proteins (as listed in Table S1 ). Docking simulations were performed as docking protocol reported elsewhere and results were reported in Table S1 35 . Visual inspection of produced docking poses (10 poses/molecule) for binding interactions with various amino acid residues lining active site of both 4MNF and 1PYE crystal structure and were listed in Table S1 and represented as 2 D and 3 D diagrams in Figures 1–2 , Figures S1–S3 .…”

Metabolomic Profiling, In Vitro Antimalarial Investigation and In Silico Modeling of the Marine Actinobacterium Strain Rhodococcus sp. UR111 Associated with the Soft Coral Nephthea sp.

“…The docking results in the form of a docking score (S; kcal/mol), docking accuracy (root-mean-square deviation; RMSD in Å), and binding interactions with various amino acid residues lining the active site were listed (as shown in Table 1 and Table 2 ). The preparation of the structural formulas of the test molecules and the structure of the target proteins were performed as reported by [ 11 ]. The validation of the prepared protein structures was conducted via the re-docking of the co-crystallized ligands with their protein crystal structure obtained from the RSCB protein data bank ( accessed on 8 August 2022), and their docking score and RMSD values were within an acceptable range for running docking simulations within the target proteins (as listed in Table 1 ).…”

“…The validation of the prepared protein structures was conducted via the re-docking of the co-crystallized ligands with their protein crystal structure obtained from the RSCB protein data bank ( accessed on 8 August 2022), and their docking score and RMSD values were within an acceptable range for running docking simulations within the target proteins (as listed in Table 1 ). The docking simulations were performed according to a docking protocol reported elsewhere [ 11 ], and the results are reported in Table 1 and Table 2 . The visual inspections of the produced docking poses (10 poses/molecule) for the binding interactions with various amino acid residues lining the active site of 3 target proteins crystal structures are listed in Table 2 and are represented as 2D and 3D diagrams.…”

Discovery of new cyanopyridine/chalcone hybrids as dual inhibitors of EGFR/BRAFV600E with promising antiproliferative properties

“…Proteins' preparation was done via the MOE LigX Protocol, while ligands were drawn using ChemDraw ® Ultra (v. 8,2003), and their energy was minimized using MMF94FX Forcefield as described elsewhere. [54][55][56] Validation of prepared proteins was performed by re-docking of cocrystallized ligands (erlotinib for 1M17 and vemurafenib for 3OG7) within their corresponding crystal structure and their docking score and RMSD were listed in Supporting Information: Table S1. Docking scores (S, kcal/mol) and root mean square deviations (RMSD, Å) for best docking poses were listed in Supporting Information: Table S1, also visual inspections of docking poses for binding modes and interactions were illustrated as 2D and 3D diagrams as in Figures 6-9.…”