title: Synthesis and Evaluation of Aminothiazole-Paeonol Derivatives as Potential Anticancer Agents.
abstract: In this study, novel aminothiazole-paeonol derivatives were synthesized and characterized using ¹H-NMR, (13)C-NMR, IR, mass spectroscopy, and high performance liquid chromatography. All the new synthesized compounds were evaluated according to their anticancer effect on seven cancer cell lines. The experimental results indicated that these compounds possess high anticancer potential regarding human gastric adenocarcinoma (AGS cells) and human colorectal adenocarcinoma (HT-29 cells). Among these compounds, N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]-4-methoxybenzenesulfonamide (13c) had the most potent inhibitory activity, with IC50 values of 4.0 µM to AGS, 4.4 µM to HT-29 cells and 5.8 µM to HeLa cells. The 4-fluoro-N-[4-(2-hydroxy-4-methoxyphenyl)thiazol-2-yl]benzenesulfonamide (13d) was the second potent compound, showing IC50 values of 7.2, 11.2 and 13.8 µM to AGS , HT-29 and HeLa cells, respectively. These compounds are superior to 5-fluorouracil (5-FU) for relatively higher potency against AGS and HT-29 human cancer cell lines along with lower cytotoxicity to fibroblasts. Novel aminothiazole-paeonol derivatives in this work might be a series of promising lead compounds to develop anticancer agents for treating gastrointestinal adenocarcinoma.
authors.affiliation: Nuclear Science &amp; Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan. s101000017@m101.nthu.edu.tw.|Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. s101000017@m101.nthu.edu.tw.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. mohitk48@gmail.com.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. suzann800217@hotmail.com.
authors.forename: Ying-Pei
authors.initials: YP
authors.lastname: Huang
authors.affiliation: Division of Radiotherapy, Department of Oncology, Taipei Veterans General Hospital, Taipei 11217, Taiwan. twwarcgogo@gmail.com.
authors.forename: Hui-Hsien
authors.initials: HH
authors.lastname: Lin
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 115, Taiwan. ycliang@sinica.edu.tw.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Liang
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan. lyring@pchome.com.tw.|Center for Bioinformatics Research, National Chiao Tung University, Hsinchu 30010, Taiwan. lyring@pchome.com.tw.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan. chin@nhri.org.tw.
authors.forename: Su-Chin
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan. wei-neng@nhri.org.tw.
authors.forename: Wei-Neng
authors.initials: WN
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli 35053, Taiwan. jkchen@nhri.org.tw.
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Chen
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. jshuang@mx.nthu.edu.tw.
authors.forename: Jer-Shing
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Nuclear Science &amp; Technology Development Center, National Tsing Hua University, Hsinchu 30013, Taiwan. mhhsu@mx.nthu.edu.twl.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Hsu
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000098:Acetophenones; D000970:Antineoplastic Agents; D013830:Thiadiazoles; C013638:paeonol; C010852:2-amino-1,3,4-thiadiazole
keywords: 2-aminothiazole; adenocarcenoma; anti-cancer; paeonol; sulfonate
references.citation: J Med Chem. 2000 Sep 21;43(19):3549-57
references.pmid: 11000009
references.citation: J Med Chem. 2001 Sep 27;44(20):3231-43
references.pmid: 11563922
references.citation: Br J Pharmacol. 2003 Jul;139(6):1146-52
references.pmid: 12871833
references.citation: BMC Pharmacol. 2005 Jun 20;5:11
references.pmid: 15963241
references.citation: J Comput Aided Mol Des. 2005 Jun;19(6):453-63
references.pmid: 16231203
references.citation: Phytomedicine. 2007 Nov;14(11):778-84
references.pmid: 17298878
references.citation: Bioorg Med Chem. 2008 Aug 15;16(16):7543-51
references.pmid: 18678492
references.citation: Anticancer Res. 2009 Jan;29(1):435-41
references.pmid: 19331183
references.citation: J Med Chem. 1990 Jan;33(1):311-7
references.pmid: 1967314
references.citation: Drug Metab Dispos. 2011 Jan;39(1):132-9
references.pmid: 20930123
references.citation: Cancer Chemother Pharmacol. 2011 Sep;68(3):795-803
references.pmid: 21193989
references.citation: J Med Chem. 2011 Jul 28;54(14):5229-36
references.pmid: 21639134
references.citation: Cancer Biol Ther. 2012 Jan 1;13(1):34-42
references.pmid: 22336586
references.citation: Evid Based Complement Alternat Med. 2012;2012:837513
references.pmid: 22454687
references.citation: Evid Based Complement Alternat Med. 2012;2012:932823
references.pmid: 22474531
references.citation: Molecules. 2012 Apr 20;17(4):4672-83
references.pmid: 22522397
references.citation: PLoS One. 2013;8(2):e56679
references.pmid: 23441212
references.citation: Acta Histochem. 2013 Oct;115(8):835-9
references.pmid: 23768958
references.citation: Am J Chin Med. 2013;41(5):1079-96
references.pmid: 24117070
references.citation: Int J Biol Macromol. 2013 Nov;62:589-95
references.pmid: 24120880
references.citation: Eur J Med Chem. 2014 Jan;71:1-14
references.pmid: 24269511
references.citation: Eur J Med Chem. 2014 Jan 24;72:26-34
references.pmid: 24333612
references.citation: Oncol Rep. 2014 Dec;32(6):2845-53
references.pmid: 25322760
references.citation: Eur J Med Chem. 2015 Jan 27;90:428-35
references.pmid: 25461891
references.citation: Molecules. 2015 Jan 14;20(1):1304-18
references.pmid: 25594344
references.citation: J Med Chem. 1997 Jul 4;40(14):2156-63
references.pmid: 9216834
references.citation: Br J Cancer. 1998 Oct;78(8):986-92
references.pmid: 9792140