Cytotoxicity 120 100 80 60 40 201 CONT. DMSO 3 10 HMC 30J. Fungi 2021, 7,Cell viability ( )HL-60 cytotoxicity120 one hundred 80 60 40 201 CONT. DMSO three ten HMC 30Figure 6. Cytotoxicity HMC for MDCK (a typical cell line) and HL-60 (a Cancer cell line). The Figure six. Cytotoxicity of of HMC for MDCK (a standard cell line) mGluR Storage & Stability andHL-60 (a Cancer cell line). The cells have been treated with HMC (1, three, ten, 30 and 50 M) for 24 h. culture supernatant was removed, cells were treated with HMC (1, 3, ten, 30 and50 ) for 24 h. The culture supernatant was reand and cell counting was was added. All information are expressed as mean common deviation moved,cell counting kit-8 kit-8 added. All data are expressed as imply standard deviation (SD) of (SD) of triplicate independent experiments. triplicate independent experiments.three.8. Molecular Docking Simulation and Molecular Dynamics three.eight. Molecular Docking Simulation and Molecular Dynamics The docking simulations showed that (S)-HMC situated properly the binding internet site of the docking simulations showed that (S)-HMC positioned properly at at the binding site of HRM complexed with MAO-A and also the the binding PIM2 manufacturer siteP1BP1B complexed with MAOHRM complexed with MAO-A and at at binding internet site of of complexed with MAO-B. B. The AutoDock Vina showed that the binding affinity of your compound for (-7.3 The AutoDock Vina showed that the binding affinity of the compound for MAO-BMAO-B (-7.3 kcal/mol) was larger than that of (-6.1 kcal/mol), and that the that the compound kcal/mol) was greater than that of MAO-AMAO-A (-6.1 kcal/mol), and compound could could interact with MAO-B by a hydrogen-bond Cys172 Cys172 residue at a of 3.656 interact with MAO-B by a hydrogen-bond with thewith the residue at a distancedistance of ,3.656 whereas no hydrogen bond interaction was predicted for (Figure 7A,B). When whereas no hydrogen bond interaction was predicted for MAO-A MAO-A (Figure 7A,B). When (R)-enantiomer was analyzed, the binding affinities for MAO-B (-7.four kcal/mol) (R)-enantiomer was analyzed, the binding affinities for MAO-B (-7.four kcal/mol) and MAOand MAO-A (-6.4 kcal/mol) had been similar or comparable to (S)-enantiomer (Figure 7C,D). A (-6.four kcal/mol) have been related or comparable to (S)-enantiomer (Figure 7C,D). To validate To validate these final results, the docking simulation with co-crystallized ligands, HRM (Ki = five these final results, the docking simulation with co-crystallized ligands, HRM (Ki = five or 17 nM) or 17 nM) and P1B (Ki = 500 nM) have been used for MAO-A and MAO-B, respectively, and their and P1B (Ki = 500 nM) had been utilised for MAO-A and MAO-B, respectively, and their binding binding scores have been calculated to become -8.1 kcal/mol and -8.7 kcal/mol, respectively scores have been calculated to become -8.1 kcal/mol and -8.7 kcal/mol, respectively (Figure 7E,F). (Figure 7E,F). Interestingly, S-enantiomer bound to a deeper position at the active web-site Interestingly, S-enantiomer bound to a deeper position at the active website of MAO-B than of MAO-B than R-enantiomer, which was positioned at a centered space, using a reverse R-enantiomer, which was positioned at a centered space, having a reverse conformation of conformation of the chiral carbon atom (Figure 7F). the chiral carbon atom (Figure 7F). In molecular dynamics, for each MAO-A and MAO-B complexes, the RMSD values In molecular dynamics, for each MAO-A and MAO-B complexes, the RMSD values enhanced and reached a stable state immediately after 125 ps. The RMSD values in complexes with enhanced and reached a steady state soon after 125 ps. The RMSD values in compl.
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