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Updated: Feb 26, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors
Qing Liu1, Xiaoqing Cai2, Dehua Yang2
1School 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.
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.
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