![]() ![]() Compounds #31, #70, #71, #72, and #73 were found to pass the ADME evaluation and throughout the screening, only compound #31 passed the predicted toxicity evaluation. Furthermore, these top hit compounds were subjected to in silico ADMETox evaluation. ![]() A significant increase on the binding affinity was observed when modifying the aglycon part instead of the sugar moiety. Results showed improved binding energy from −6.00 to −8.00 kcal mol −1. The synthesized and newly designed compounds were subjected to 3D-QSAR to further design compounds with effective interaction within the active site. Interestingly, the analogs of the known disaccharide substrate, compounds #1–4, have binding energy range of −10.00 to −19.00 kcal mol −1. These compounds were synthesized as UDP-Galactopyranose mutase (UGM) inhibitors and could possibly inhibit GlfT2. Two compounds, #27 and #31, have registered binding energy values of −8.32 ± 0.01, and −8.08 ± 0.01 kcal mol −1, respectively. Molecular docking studies showed that the synthesized compounds have binding energy values between −3.00 to −6.00 kcal mol −1. With the current challenge of designing potential GlfT2 inhibitors with high inhibition activity, computational methods such as molecular docking, receptor-ligand mapping, molecular dynamics, and Three-Dimensional-Quantitative Structure-Activity Relationship (3D-QSAR) were utilized to deduce the interactions of the reported compounds with the target enzyme and enabling the design of more potent GlfT2 inhibitors. Studies targeting GlfT2 have so far produced compounds showing minimal inhibitory activity. One of these enzymes is Galactofuranosyltransferase 2 (GlfT2) that catalyzes the elongation of the galactan chain of Mtb cell wall. A strategy in the discovery of anti-tuberculosis (anti-TB) drug involves targeting the enzymes involved in the biosynthesis of Mycobacterium tuberculosis’ ( Mtb) cell wall. ![]()
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