title: Bis(pentafluorosulfanyl)phenyl azide as an expeditious tool for click chemistry toward antitumor pharmaceuticals.
abstract: The inclusion of fluorine in pharmaceutical agents is a well- established means of improving their druglike properties. Different substituents have been used to introduce fluorine, including trifluoromethyl and trifluoromethylthio groups; however, the pentafluorosulfanyl remains relatively underutilized although it is considered to be a "super" trifluoromethyl group. Here, a series of pentafluorosulfanyl-containing 1,4-disubstituted-1,2,3-triazoles were synthesized by click reaction from alkynes and 3,5-bis(pentafluorosulfanyl)phenyl azide in excellent yields. Their biological activities were evaluated against human leukemic monocyte lymphoma U937 cells. In particular, 1-(3,5-bis(pentafluorosulfanyl)phenyl)-4-(4-fluorophenyl)-1H-1,2,3-triazole exhibited potent efficacy in cell viability assays at a concentration of 60 μM and was shown to activate caspase-3 activity, indicating induction of apoptosis. An analogous fluorenol-substituted triazole also exhibited promising cytotoxic effects against U937 cells, with an IC50 value of 6.29 μM. Given these preliminary results, these pentafluorosulfanyl-containing triazoles represent useful building blocks for the further development of novel antitumor agents.
authors.affiliation: Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555 (Japan).
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Yang
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tokunaga
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Norimichi
authors.initials: N
authors.lastname: Saito
authors.forename: Norio
authors.initials: N
authors.lastname: Shibata
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001386:Azides / Q000737:chemistry*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry*; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D001386:Azides; D013440:Sulfides; D053148:Caspase 3
keywords: antitumor agents; apoptosis; necrosis; pentafluorosulfanyl group; triazoles