In:
New Journal of Chemistry, Royal Society of Chemistry (RSC), Vol. 46, No. 40 ( 2022), p. 19342-19356
Abstract:
Cyclin-dependent kinase 9 (CDK9) has been identified as an important drug target for the treatment of cancers. Herein, we report the discovery of a series of tacrine-based CDK9 inhibitors with nanomolar inhibitory potency against CDK9, good selectivity over CDK2, and weaker acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition. Among these, compound ZLWT-48 possessed promising antiproliferative activity (GI 50 = 0.889 μM for HCT116), potent CDK9 inhibition (IC 50 = 8.639 nM), and excellent selectivity over CDK2 (IC 50 〉 500 nM, Selectivity Index 〉 57). In addition, ZLWT-48 exhibited lower inhibitory activity against AChE and BuChE compared to the parent compound tacrine. The in vitro studies demonstrated that ZLWT-48 could significantly inhibit cell proliferation, induce apoptosis, suppress migration, and block invasion in HCT116 cells. These findings indicated that compound ZLWT-48 was a potential lead compound as a CDK9 inhibitor that deserves further structural modification for the treatment of cancer.
Type of Medium:
Online Resource
ISSN:
1144-0546
,
1369-9261
Language:
English
Publisher:
Royal Society of Chemistry (RSC)
Publication Date:
2022
detail.hit.zdb_id:
622959-1
detail.hit.zdb_id:
1472933-7
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