Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors.

Liu, Qing; Cai, Xiaoqing; Yang, Dehua; Chen, Yi; Wang, Yafang; Shao, Liming; Wang, Ming-Wei

Liu, Qing; Cai, Xiaoqing; Yang, Dehua; Chen, Yi; Wang, Yafang; Shao, Liming; Wang, Ming-Wei.

Afiliación

Liu Q; School of Pharmacy, Fudan University, Shanghai 201203, China; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; The National Center for Drug Screening, Shanghai 201203, China.
Cai X; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; The National Center for Drug Screening, Shanghai 201203, China.
Yang D; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; The National Center for Drug Screening, Shanghai 201203, China.
Chen Y; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Wang Y; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Shao L; School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: limingshao@fudan.edu.cn.
Wang MW; School of Pharmacy, Fudan University, Shanghai 201203, China; The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; The National Center for Drug Screening, Shanghai 201203, China; Shanghai Institute of Materia Medica,

Bioorg Med Chem ; 25(17): 4579-4594, 2017 09 01.

Article en En | MEDLINE | ID: mdl-28739157

ABSTRACT

ABSTRACT

A series of cycloalkyl substituted analogues of the natural product sinefungin lacking the amino-acid moiety was designed and synthesized. Two stereoisomers (6-R and 6-S) were separated and their bioactivities examined against EHMT1/2. Of which, compound 14d showed an inhibitory activity against EHMT1/2 (88.9%, IC50=21.8µM for EHMT1 and 77.6%, IC50=39.6µM for EHMT2, respectively) similar to that of sinefungin (100.0%, IC50=28.4µM for EHMT1 and 79.5%, IC50=30.1µM for EHMT2, respectively). Further studies against other methyltransferases such as PRMT1 showed no activity except that 12d displayed about 20% inhibition.

Asunto(s)

Adenosina/análogos & derivados; Inhibidores Enzimáticos/química; N-Metiltransferasa de Histona-Lisina/antagonistas & inhibidores; Adenosina/química; Adenosina/metabolismo; Adenosina/toxicidad; Alcanos/química; Línea Celular Tumoral; Proliferación Celular/efectos de los fármacos; Inhibidores Enzimáticos/metabolismo; Inhibidores Enzimáticos/toxicidad; Antígenos de Histocompatibilidad/metabolismo; N-Metiltransferasa de Histona-Lisina/metabolismo; Humanos; Concentración 50 Inhibidora; Relación Estructura-Actividad

Palabras clave

Cycloalkyl substituted analogue; Methyltransferase inhibitor; Natural product; Sinefungin

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Adenosina / N-Metiltransferasa de Histona-Lisina / Inhibidores Enzimáticos Límite: Humans Idioma: En Revista: Bioorg Med Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2017 Tipo del documento: Article País de afiliación: China

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