Molecular Docking of Andrographoilde and HDAC2 inhibitor an approach to manage for Beta Thalassemia

Abstract

Beta thalassemia is a disorder of globin gene synthesis resulting in the absent production of beta globin chain in RBC. The property of inducing gamma globin gene expression by the search for bioactive compounds exhibiting is of great interest. Regulation of HDAC activity by dietary flavones couldhave important implication in developing epigenetic therapy to regulate the cell geneexpression. Several pharmacological agents have been identified overthe past two decades that reactivate gamma globin gene transcription through differentcellular system. We will search for the complementary and alternative medicine (CAM)which regulated switch from fetal to adult globin gene expression could be prevented hasresult in the development of new class of therapeutic agent consisting of some bioactivecompounds such as flavanone for the treatment of beta thalassemia. Flavones one suchmolecule of plant origin are known to interfere with HDAC2 enzyme and to enhance theacetylation restoring cell homeostasis, p38 MAPK pathway. Induction of HbF expression inerythroid cells is an important and another therapeutic approach in beta thalassemia. We used Schrodinger suites to develop computational approaches for estimating drug and target binding affinities. The target enzyme's sequence alignments contain 539 amino acid residues, and bioactive compounds that act as ligand molecules were acquired from the plant Andrographis paniculata. We used molecular docking, and ADME analysis. The current study explores the binding pattern of Andrographoilde and Vorinostat (SAHA) against their target protein (PDBIDs: 6G3O), respectively using molecular docking approaches. The molecular docking results show that Andrographoilde binds within the active region of HDAC2 inhibitors by forming hydrogen bonds against ASP104 and TYR 308 respectively. However, the Vorinostat interacts with TYR 308 and GLY 142respectively. Our comparative results show that andrographoilde may be a similar therapeutic agent for managing beta thalassemia as compare to vorinostat. However, functional studies are needed to confirm their proposed relevance in beta thalassemia in vitro and in vivo evaluation studies are required.