Identification of potent virtual leads to design novel indoleamine 2,3-dioxygenase inhibitors: pharmacophore modeling and molecular docking studies.
Indoleamine 2,3-dioxygenase, a heme-containing enzyme, is emerging as a vital target for the treatment of cancer, chronic viral infections, and other diseases. The aim of this study is to identify novel scaffolds and utilize them in designing potent IDO inhibitors. Pharmacophore hypotheses were developed. The highly correlating (r = 0.958) hypothesis with two hydrogen bond acceptor, one hydrogen bond donor and one hydrophobic aromatic features was selected, validated and used in virtual screening. Hit compounds were subjected to various drug-like filtrations and molecular docking studies. Finally, three structurally diverse compounds with high GOLD fitness scores and interactions with critical active site amino acids were identified. These final hits may act as potent virtual leads in effective IDO inhibitor designing.
John
Shalini
S
Department of Biochemistry and Division of Applied Life Science (BK21 Program), Environmental Biotechnology National Core Research Center, Gyeongsang National University, 900 Gazwa-dong, Jinju 660-701, Republic of Korea.
Thangapandian
Sundarapandian
S
Sakkiah
Sugunadevi
S
Lee
Keun Woo
KW
D016208:Databases, Factual; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D015203:Reproducibility of Results; D014584:User-Computer Interface
D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase