In:
Chemistry & Biodiversity, Wiley, Vol. 20, No. 5 ( 2023-05)
Abstract:
Herein, we report the design, synthesis and evaluation of novel ( E )‐3‐(3‐oxo‐4‐substituted‐3,4‐dihydro‐2H‐benzo[b][1,4] oxazin‐6‐yl)‐ N ‐hydroxypropenamides ( 4 a – i , 7 a – g ) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC‐3, prostate; NCI−H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a – i bearing the alkyl substituents seemed to be less potent than the benzyl‐containing compounds 7 a – g in all biological assays. Compounds 7 e – f were found to be the most active HDAC inhibitors with IC 50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC 50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity.
Type of Medium:
Online Resource
ISSN:
1612-1872
,
1612-1880
DOI:
10.1002/cbdv.202201030
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2139001-0
SSG:
12
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