title: Discovery and structure-activity relationships of phenyl benzenesulfonylhydrazides as novel indoleamine 2,3-dioxygenase inhibitors.
abstract: A novel class of phenyl benzenesulfonylhydrazides has been identified as potent inhibitors of indoleamine 2,3-dioxygenase (IDO), and their structure-activity relationship was explored. Coupling reactions between various benzenesulfonyl chlorides and phenylhydrazides were utilized to synthesize the sulfonylhydrazides bearing various substituents. Compound 3i exhibited 61 nM of IC50 in enzymatic assay and 172 nM of EC50 in the HeLa cell. The computational study of 3i suggested that the major interactions between 3i and IDO protein are the coordination of sulfone and heme iron, the hydrogen bonding and hydrophobic interactions between 3i and IDO. This novel class of IDO inhibitor provides a new direction to discover effective anti-cancer agents.
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Cheng
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Ming-Shiu
authors.initials: MS
authors.lastname: Hung
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Fang-Yu
authors.initials: FY
authors.lastname: Liao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Mine-Hsine
authors.initials: MH
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Wenchi
authors.initials: W
authors.lastname: Hsiao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Chia-Ling
authors.initials: CL
authors.lastname: Hsieh
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Jian-Sung
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC.
authors.forename: Chuan
authors.initials: C
authors.lastname: Shih
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC. Electronic address: suying@nhri.org.tw.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Wu
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, ROC. Electronic address: shueng@nhri.org.tw.
authors.forename: Shau-Hua
authors.initials: SH
authors.lastname: Ueng
mesh_terms: D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010659:Phenylhydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000595743:4-((2-(4-bromophenyl)hydrazinyl)sulfonyl)benzoic acid; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010659:Phenylhydrazines; D013449:Sulfonamides
keywords: Indoleamine 2,3-dioxygenase; Molecular docking; Structure–activity relationship; Sulfonylhydrazide