Portal de investigación
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity
Autores de INCLIVA
Participantes ajenos a INCLIVA
- Vettorazzi, M
- Lima, S
- Acosta, L
- Yepes, F
- Palma, A
- Cobo, J
- Tengler, J
- Malik, I
- Alvarez, S
- Marques, P
- Jampilek, J
- Spiegel, S
- Enriz, RD
Grupos y Plataformas de I+D+i
Abstract
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7-bromo-2-(2-phenylethyl)-2,3,4,5-tetrahydro-1,4-epoxynaphtho[1,2-b]azep ine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti-inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil-endothelial cell interactions. The information obtained from our theoretical and experimental study can be useful in the search for inhibitors of SphK2 that play a prominent role in different diseases, especially in inflammatory and cardiovascular disorders.
© 2019 Deutsche Pharmazeutische Gesellschaft
Datos de la publicación
- ISSN/ISSNe:
- 0365-6233, 1521-4184
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 30648282
ARCHIV DER PHARMAZIE WILEY-V C H VERLAG GMBH
Citas Recibidas en Web of Science: 8
Documentos
- No hay documentos
Filiaciones
Keywords
- anti-inflammatory activity; bioassays; molecular modeling; sphingosine kinase 2 inhibitors; synthesis
Financiación
Proyectos y Estudios Clínicos
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SAF2014-57845-R . MINISTERIO ECONOMIA Y COMPETITIVIDAD . 2015
Synthesis and pharmacological evaluation of new dual PPARalpha/gamma agonists as new therapeutic tools in the control of cardiometabolic disorders
Investigador Principal: NURIA CABEDO ESCRIG
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RETOS 2017. MODULACION FARMACOLOGICA DEL SISTEMA INMUNE COMO DIANA CLAVE EN LA PREVENCION DE LA ENFERMEDAD CARDIOVASCULAR ASOCIADA A DESORDENES METABOLICOS. SINTESIS DE FARMACOS NOVEDOSOS
Investigador Principal: MARIA JESUS SANZ FERRANDO
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Cita
Vettorazzi M,Vila L,Lima S,Acosta L,Yepes F,Palma A,Cobo J,Tengler J,Malik I,Alvarez S,Marques P,Cabedo N,Sanz MJ,Jampilek J,Spiegel S,Enriz RD. Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity. Arch Pharm (Weinheim). 2019. 352. (3):1800298. IF:2,590. (2).
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity. Vettorazzi M, Vila L, Lima S, Acosta L, Yepes F, Palma A, Cobo J et al. ARCHIV DER PHARMAZIE. 2019 marzo 01. 352 (3):DOI:10.1002/ardp.201800298. PMID:30648282.
