New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine Derivatives as Potential Inhibitors of Adenovirus Infection. Synthesis, Biological Evaluation, and Structure-activity Relationships

被引:30
作者
Sanchez-Cespedes, Javier [1 ]
Martinez-Aguado, Pablo [1 ]
Vega-Holm, Margarita [2 ]
Serna-Gallego, Ana [1 ]
Ignacio Candela, Jose [2 ]
Antonio Marrugal-Lorenzo, Jose [1 ]
Pachon, Jeronimo [1 ,3 ]
Iglesias-Guerra, Fernando [2 ]
Manuel Vega-Perez, Jose [2 ]
机构
[1] Univ Seville, Unit Infect Dis Microbiol & Prevent Med, Inst Biomed Seville IBiS, Univ Hosp Virgen Rocio,CSIC, E-41013 Seville, Spain
[2] Univ Seville, Dept Organ & Med Chem, Fac Pharm, Prof Garcia Gonzalez 2, E-41071 Seville, Spain
[3] Univ Seville, Dept Med, E-41009 Seville, Spain
关键词
ORGAN TRANSPLANT RECIPIENTS; ENTRY INHIBITORS; IN-VITRO; VIRAL-INFECTIONS; VIRUS-INFECTION; REPLICATION; ANALOGS; FUSION; CELLS; CYTOMEGALOVIRUS;
D O I
10.1021/acs.jmedchem.6b00300
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The search for human adenovirus (HAdV)-specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients continues to be a challenging goal for medicinal chemistry. Here, we report the synthesis, biological evaluation, and structure activity relationships of a small molecules library. We have identified six phenylpiperazine derivatives that significantly inhibited HAdV infection. These six compounds showed the capacity to block HAdV and, in addition, human cytomegalovirus (HCMV) replications at low micromolar concentration, with little or no cytotoxicity. On the basis of our biological studies, these molecules block HAdV and HCMV infections in different phases of their life cycle, providing potential candidates for the development of a new family of antiviral drugs for the treatment of infections by DNA viruses.
引用
收藏
页码:5432 / 5448
页数:17
相关论文
共 51 条
[41]   Kinesin-1-Mediated Capsid Disassembly and Disruption of the Nuclear Pore Complex Promote Virus Infection [J].
Strunze, Sten ;
Engelke, Martin F. ;
Wang, I-Hsuan ;
Puntener, Daniel ;
Boucke, Karin ;
Schleich, Sibylle ;
Way, Michael ;
Schoenenberger, Philipp ;
Burckhardt, Christoph J. ;
Greber, Urs F. .
CELL HOST & MICROBE, 2011, 10 (03) :210-223
[42]   Adenovirus: An Overview for Pediatric Infectious Diseases Specialists [J].
Tebruegge, Marc ;
Curtis, Nigel .
PEDIATRIC INFECTIOUS DISEASE JOURNAL, 2012, 31 (06) :626-627
[43]   Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model [J].
Toth, Karoly ;
Spencer, Jacqueline F. ;
Dhar, Debanjan ;
Sagartz, John E. ;
Buller, R. Mark L. ;
Painter, George R. ;
Wold, William S. M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (20) :7293-7297
[44]   Aziridines from alkenyl-β-D-galactopyranoside derivatives: Stereoselective synthesis and in vitro selective anticancer activity [J].
Vega-Perez, Jose M. ;
Palo-Nieto, Carlos ;
Vega-Holm, Margarita ;
Gongora-Vargas, Purificacion ;
Manuel Calderon-Montano, Jose ;
Burgos-Moron, Estefania ;
Lopez-Lazaro, Miguel ;
Iglesias-Guerra, Fernando .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 70 :380-392
[45]   Isoprenyl-thiourea and urea derivatives as new farnesyl diphosphate analogues: Synthesis and in vitro antimicrobial and cytotoxic activities [J].
Vega-Perez, Jose M. ;
Perinan, Ignacio ;
Argandona, Montserrat ;
Vega-Holm, Margarita ;
Palo-Nieto, Carlos ;
Burgos-Moron, Estefania ;
Lopez-Lazaro, Miguel ;
Vargas, Carmen ;
Nieto, Joaquin J. ;
Iglesias-Guerra, Fernando .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 58 :591-612
[46]   Stereoselective Dihydroxylation Reaction of Alkenyl ß-D-Hexopyranosides: A Methodology for the Synthesis of Glycosylglycerol Derivatives and 1-O-Acyl-3-O-ß-D-glycosyl-sn-glycerol Analogues [J].
Vega-Perez, Jose M. ;
Palo-Nieto, Carlos ;
Perinan, Ignacio ;
Vega-Holm, Margarita ;
Calderon-Montano, Jose M. ;
Lopez-Lazaro, Miguel ;
Iglesias-Guerra, Fernando .
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2012, 2012 (06) :1237-1252
[47]   Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience [J].
Verdeguer, A. ;
de Heredia, C. D. ;
Gonzalez, M. ;
Martinez, A. M. ;
Fernandez-Navarro, J. M. ;
Perez-Hurtado, J. M. ;
Badell, I. ;
Gomez, P. ;
Gonzalez, M. E. ;
Munoz, A. ;
Diaz, M. A. .
BONE MARROW TRANSPLANTATION, 2011, 46 (01) :119-124
[48]   Inhibitors of HIV-1 attachment. Part 4: A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives [J].
Wang, Tao ;
Kadow, John F. ;
Zhang, Zhongxing ;
Yin, Zhiwei ;
Gao, Qi ;
Wu, Dedong ;
Parker, Dawn DiGiugno ;
Yang, Zheng ;
Zadjura, Lisa ;
Robinson, Brett A. ;
Gong, Yi-Fei ;
Blair, Wade S. ;
Shi, Pei-Yong ;
Yamanaka, Gregory ;
Lin, Pin-Fang ;
Meanwell, Nicholas A. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (17) :5140-5145
[49]   Characterization of lassa virus cell entry inhibitors: Determination of the active enantiomer by asymmetric synthesis [J].
Whitby, Landon R. ;
Lee, Andrew M. ;
Kunz, Stefan ;
Oldstone, Michael B. A. ;
Boger, Dale L. .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (14) :3771-3774
[50]   Preclinical Characterization of GLS4, an Inhibitor of Hepatitis B Virus Core Particle Assembly [J].
Wu, Guoyi ;
Liu, Bo ;
Zhang, Yingjun ;
Li, Jing ;
Arzumanyan, Alla ;
Clayton, Marcia M. ;
Schinazi, Raymond F. ;
Wang, Zhaohe ;
Goldmann, Siegfried ;
Ren, Qingyun ;
Zhang, Faxhou ;
Feitelson, Mark A. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2013, 57 (11) :5344-5354