title: Synthesis of Novel Chiral Sulfonamide-Bearing 1,2,4-Triazole-3-thione Analogs Derived from D- and L-Phenylalanine Esters as Potential Anti-Influenza Agents.
abstract: Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, (1) H NMR, (13) C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in (R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds , , , , and (EC50 : 6.5, 6.1, 2.4, 1.6, 1.7 μM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50 : 8.0 μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53 μM range. Compound and in (R) configuration were the most active compounds (IC50 : 12-22 μM for and IC50 : 19-23 μM for ). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Gaziantep University, Faculty of Science and Arts, Department of Chemistry, Gaziantep, Turkey.
authors.forename: Eyüp
authors.initials: E
authors.lastname: Başaran
authors.affiliation: Gaziantep University, Faculty of Science and Arts, Department of Chemistry, Gaziantep, Turkey.
authors.forename: Ayşegül
authors.initials: A
authors.lastname: Karaküçük-Iyidoğan
authors.affiliation: Rega Institute forMedical Research, KU Leuven, Leuven, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Schols
authors.affiliation: Gaziantep University, Faculty of Science and Arts, Department of Chemistry, Gaziantep, Turkey.
authors.forename: Emine Elçin
authors.initials: EE
authors.lastname: Oruç-Emre
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects; D061985:Madin Darby Canine Kidney Cells; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; C505757:L-phenylalanine ethylester; D013449:Sulfonamides; D014230:Triazoles; C034515:phenylalanine methyl ester; C045575:1,2,4-triazole; D010649:Phenylalanine
keywords: H1N1; antiviral; chiral 1,2,4-triazole-3-thiones; cytostatic; influenza A; sulfonamide