Ing) and to decipher their ligand rotein interaction with COX-1/2. Molecular
Ing) and to decipher their ligand rotein interaction with COX-1/2. Molecular dynamics simulationMolecules 2021, 26, x FOR PEER REVIEWMolecules 2021, 26,3 of3 ofdocking) and to decipher their ligand rotein interaction with COX-1/2. Molecular dynamics simulation experiments and binding energy calculations were performed to idenexperiments and binding power calculations had been performed to determine the stability and tify the stability and compactness on the chosen ligand rotein complex. Comparative compactness in the chosen ligand rotein complicated. Comparative analysis was performed analysis was performed against aspirin (Figure 1a), the chosen FDA-approved, extensively against aspirin (Figure 1a), the chosen FDA-approved, extensively made use of, and oldest antiused, and oldest anti-inflammatory lead molecule [38,39]. Furthermore, we characterized inflammatory lead molecule [38,39]. In addition, we characterized their pharmacokinetic their pharmacokinetic and toxicokinetic profiles to predict the bioactivity and security of and toxicokinetic profiles to predict the bioactivity and security of these brominated indoles. these brominated indoles.Figure 1. The 2D structure the ligands applied in in study. (a) (a) aspirin, (b) tyrindoxyl sulfate, (c) tyrindoleninone, Figure 1. The 2D structure of on the ligands usedthis this study.aspirin, (b) tyrindoxyl sulfate, (c) tyrindoleninone, (d) 6-bromoisatin, and (e) 6,six dibromoindirubin. six,6dibromoindirubin.Molecules 2021, 26,four of2. Final results and Discussion 2.1. Molecular Docking Analysis Molecular docking is usually a standard approach for structure-based drug design and style to evaluate the atomic level interaction between smaller molecules along with a protein; hence, it aids to determine target specificity in addition to binding affinity [402]. Molecular docking studies, employed right here by means of GLIDE, predict the binding affinity from the 3D structure of D. orbita secondary metabolites into a cyclooxygenase isoform COX-1 (Figure two) and COX-2 binding site (Figure 3). The outcomes of the GLIDE scores, GLIDE energy, GLIDE model, and GLIDE ligand in the docking analyses are presented in Tables 1 and two for COX-1 and COX-2, respectively. As shown in Table 1, the docking score range for the mollusk brominated indoles was -6.06 to -7.25 kcal/mol for COX-1, which is comparatively much better than the Pseudoerythromycin A enol ether Epigenetics reference compound aspirin (-2.80 kcal/mol). Alternatively, the docking score of aspirin was -6.87 kcal/mol using the COX-2 enzyme, which was related for the indole derivatives tyrindoxyl sulfate (-6.34 kcal/mol) and 6-bromoisatin (-6.19 kcal/mol). Furthermore, tyrindoleninone showed a higher binding affinity toward COX-2, with a docking score of -7.17 kcal/mol. Interestingly, 6,six dibromoindirubin exhibited a high binding Molecules 2021, 26, x FOR PEER Critique five of 27 affinity to COX-1, plus the docking score was -7.25 kcal/mol, whereas the docking score of this compound was only -3.14 kcal/mol for COX-2.Figure two. 3D interaction maps (distances of Dicathais orbita brominated indole derivatives and typical aspirin Butachlor Technical Information displaying the crystallographic ligand having a COX-1 active binding internet site; (a) aspirin, (b) tyrindoxyl sulfate, (c) tyrindoleninone, Figure 2. 3D interaction maps (distances of Dicathais orbita brominated indole derivatives and common aspirin showing (d) 6-bromoisatin, and (e) six,six -dibromoindirubin.binding web page; (a) aspirin, (b) tyrindoxyl sulfate, (c) tyrindoleninone, (d) 6the crystallographic ligand using a COX-1 activebromoisatin, and (e) 6,6′-dibromoindirubi.
