@article{c6f98c202e4c4a1493995cf7810b298f,
title = "Synthesis and biological evaluation of phenothiazine derivative-containing hydroxamic acids as potent class II histone deacetylase inhibitors",
abstract = "The pathogenesis of Alzheimer's disease (AD) has been associated with dysregulation of histone deacetylases (HDACs). Previously, acridine-based HDAC inhibitors have shown potential in ameliorating HDAC activity and enhancing neurite outgrowth. In this study, the acridine ring was modified using various phenothiazine derivatives. Several resulting compounds exhibited potent enzyme-inhibiting activity towards class II HDACs when compared to the clinically approved HDAC inhibitor SAHA. Compound 4f demonstrated the highest class II HDAC inhibition (IC50 = 4.6–600 nM), as well as promotion of neurite outgrowth. Importantly, compound 4f displayed no cytotoxicity against neuron cells. Compound 4f was further evaluated for cellular effects. Altogether, these findings show a potential strategy in HDAC inhibition for treatment of the neurological disease.",
keywords = "Alzheimer's disease, Histone deacetylase, Neurite outgrowth, Phenothiazine",
author = "Kai-Cheng Hsu and Jung-Chun Chu and Hui-Ju Tseng and Chia-I Liu and Hao-Ching Wang and Lin, {Tony Eight} and Hong-Sheng Lee and Ling-Wei Hsin and Wang, {Andrew H.-J.} and Chien-Huang Lin and Wei-Jan Huang",
note = "Funding Information: We gratefully acknowledge the support from the Ministry of Science and Technology ( MOST108-2320-B-038 -036 and MOST108-2320-B-038-058-MY3 ) in Taiwan. This research was also partially supported by the Taiwan Protein Project (Grant No. MOST105-0210-01-12-01 and Grant No. MOST106-0210-01-15-04 ). Publisher Copyright: {\textcopyright} 2021 Elsevier Masson SAS",
year = "2021",
month = jul,
day = "5",
doi = "10.1016/j.ejmech.2021.113419",
language = "English",
volume = "219",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson s.r.l.",
}