Antiviral activity and molecular modeling studies on 1H-indole-2,3-diones carrying a naphthalene moiety


SOYLU ETER Ö., Duran G. N., Özbil M., GÖKTAŞ F., CİHAN ÜSTÜNDAĞ G., KARALI N. L.

JOURNAL OF MOLECULAR STRUCTURE, vol.1281, 2023 (SCI-Expanded, Scopus)

  • Publication Type: Article / Article
  • Volume: 1281
  • Publication Date: 2023
  • Doi Number: 10.1016/j.molstruc.2023.135100
  • Journal Name: JOURNAL OF MOLECULAR STRUCTURE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chemical Abstracts Core, Chimica, Compendex, INSPEC
  • Keywords: 1H-indole-2,3-dione, Antiviral activity, Herpes simplex viruses, Molecular modeling, Naphthalene, Respiratory syncytial virus, Vesicular stomatitis virus
  • Istanbul University Affiliated: Yes

Abstract

We here report the synthesis, structural characterization, and evaluation of the in vitro antiviral effects of a series of 1H-indole-2,3-diones ( 2a -f ) bearing a naphthalene moiety. All 1-(naphthalen-2-ylmethyl)-1H- indole-2,3-diones ( 2c-f ) tested against different herpes simplex viruses (HSVs) were found to be effective at low micromolar levels (EC50 = 2.3-20.0 mu M). Molecular dynamics and docking simulations were per-formed with compound 2d which exhibited the strongest activity against HSVs and the binding affinities for HSV-1 surface glycoproteins B (gB) and D (gD) were calculated. Moreover, 5-bromo-1-(naphthalen-1-ylmethyl)-1H-indole-2,3-dione ( 2b ) and 1-(naphthalen-2-ylmethyl)-1H-indole-2,3-dione ( 2c ) exhibited nontoxic antiviral effects (EC50 = 6.8-12.0 mu M) against vesicular stomatitis virus (VSV) and respiratory syn-cytial virus (RSV). To examine the contribution of the naphthalene ring, 1-methyl or 1-ethyl substituted compounds (2g-i) were also evaluated for in vitro antiviral activity, but these derivatives showed no an-tiviral activity against any of the viruses tested. (c) 2023 Elsevier B.V. All rights reserved.