title: Structure-activity relationships (SAR) research of thiourea derivatives as dual inhibitors targeting both HIV-1 capsid and human cyclophilin A.
abstract: HIV-1 capsid (CA) and human cyclophilin A (CypA) play important roles in HIV-1 assembly and disassembly processes, which are critical in HIV-1 replication. Based on the discovery of thiourea derivatives targeting both of the two proteins and indicating effective inhibitory activities in our group, we designed and synthesized a new class of thiourea derivatives. Their abilities to bind to capsid and cyclophilin A were determined by ultraviolet spectroscopic analysis, fluorescence binding affinity, and PPIase inhibition assay. Furthermore, the newly synthesized compounds were tested for their antiviral activities and cytotoxicities using CEM cells. According to the biological evaluation and subsequent molecular docking analyses, we studied the structure-activity relationships of thiourea derivatives. Three optimal compounds (K17, K24, K25) based on the achieved structure-activity relationships would be the basis for future optimization.
authors.affiliation: The State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Tan
authors.forename: Meizi
authors.initials: M
authors.lastname: He
authors.forename: Jiebo
authors.initials: J
authors.lastname: Li
authors.forename: Shixing
authors.initials: S
authors.lastname: Tang
authors.forename: Indira
authors.initials: I
authors.lastname: Hewlett
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Yinxue
authors.initials: Y
authors.lastname: Jin
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D002213:Capsid / Q000737:chemistry / Q000187:drug effects; D036022:Capsid Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D021984:Cyclophilin A / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D036022:Capsid Proteins; D021984:Cyclophilin A; D013890:Thiourea