title: Design, Synthesis, and Anti-HIV Evaluation of Novel Triazine Derivatives Targeting the Entrance Channel of the NNRTI Binding Pocket.
abstract: A novel series of triazine derivatives targeting the entrance channel of the HIV-1 non-nucleoside reverse transcriptase inhibitor binding pocket (NNIBP) were designed and synthesized on the basis of our previous work. The results of a cell-based antiviral screening assay indicated that most compounds showed good-to-moderate activity against wild-type HIV-1 with EC50 values within the concentration range of 0.0078-0.16 μm (compound DCS-a4, EC50  = 7.8 nm). Some compounds displayed submicromolar activity against the K103N/Y181C resistant mutant strain (such as compound DCS-a4, EC50  = 0.65 μm). Molecular modeling studies confirmed that the new compounds could bind into the NNIBP similarly as the lead compound, and the newly introduced flexible heterocycles could occupy the entrance channel effectively. In addition, the preliminary structure-activity relationship and the RT inhibitory assay are presented in this study.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Ji'nan, Shandong, 250012, China.
authors.forename: Xuwang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Ji'nan, Shandong, 250012, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Meng
authors.affiliation: Department of Pharmacy, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, 250013, China.
authors.forename: Liyun
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Ji'nan, Shandong, 250012, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Institute of Pharmacology, School of Medicine, Shandong University, 44, West Culture Road, Ji'nan, Shandong, 250012, China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Liu
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Ji'nan, Shandong, 250012, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry; D015497:HIV-1 / Q000201:enzymology*; D062105:Molecular Docking Simulation; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D014227:Triazines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase
keywords: HIV-1; NNRTIs; antiviral activity; entrance channel; molecular modeling