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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
Author(s) -
Başaran Eyüp,
KaraküçükIyidoğan Ayşegül,
Schols Dominique,
OruçEmre Emine Elçin
Publication year - 2016
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22607
Subject(s) - chemistry , hela , enantiopure drug , stereochemistry , chirality (physics) , enantiomer , moiety , phenylalanine , in vitro , enantioselective synthesis , biochemistry , amino acid , chiral symmetry breaking , physics , quantum mechanics , quark , nambu–jona lasinio model , catalysis
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 18a , 21a , 22a , 23a , and 24a (EC 50 : 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 (EC 50 : 8.0 μM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC 50 in the 12–53 μM range. Compound 5a and 27a in ( R ) configuration were the most active compounds (IC 50 : 12–22 μM for 5a and IC 50 : 19–23 μM for 27a ). Chirality 28:495–513, 2016 . © 2016 Wiley Periodicals, Inc.