@article{3020348,
    title = "Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors",
    author = "Mousa, M.H.A. and Ahmed, N.S. and Schwedtmann, K. and Frakolaki, E. and Vassilaki, N. and Zoidis, G. and Weigand, J.J. and Abadi, A.H.",
    journal = "Pharmaceutics",
    year = "2021",
    volume = "14",
    number = "4",
    publisher = "MDPI AG",
    issn = "1999-4923",
    doi = "10.3390/ph14040292",
    keywords = "adenosine triphosphate;  daclatasvir;  diamine derivative;  fluorene 2,7 diamine derivative;  isoleucine;  nonstructural protein 5A inhibitor;  phenylglycine;  prolinamide;  unclassified drug, antiviral activity;  Article;  chemical modification;  controlled study;  cytotoxicity assay;  drug design;  drug selectivity;  drug structure;  drug synthesis;  EC50;  gel electrophoresis;  Hepatitis C virus subtype 1b;  high performance liquid chromatography;  human;  human cell;  luciferase assay;  mass spectrometry;  nonhuman;  RNA extraction;  structure activity relation;  Western blotting",
    abstract = "Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group. © 2021 by the authors."
}