Simulated human digestion of N1-aryl-2-arylthioacetamidobenzimidazoles and their activity against Herpes-simplex virus 1 in vitro

PLoS One. 2019 May 2;14(5):e0216384. doi: 10.1371/journal.pone.0216384. eCollection 2019.

Abstract

Drug performance in the gastrointestinal tract (GIT) plays a crucial role in determining release and absorption. In the present work, we assessed the in vitro digestion of two synthetic N1-aryl-2-arylthioacetamidobenzimidazoles (NAABs), NAAB-496 and NAAB-503, using bio-relevant models of the human stomach and small intestine. The activity of NAAB-496 and NAAB-503 against herpes simplex virus (HSV-1) replication was also investigated. NAAB-496 was resistant to pepsin in the gastric environment, with a virtual 100% recovery, which decreased to 43.2% in the small intestine. NAAB-503 was sensitive to pepsin, with 65.7% degradation after 120 min gastric phase. 1H Nuclear magnetic resonance (NMR) post in vitro digestion highlighted an alteration of NAAB-496 after the gastric phase, whereas NAAB-503 appeared comparable to the original spectral data. Both NAAB-496 and NAAB-503 revealed some antiviral activity anti-HSV-1. The 50% effective concentration (EC50) of the compounds was 0.058 mg/mL for NAAB-496 and 0.066 for NAAB-503. Future studies will evaluate the behavior of NAAB-496 within pharmaceutical formulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents* / chemistry
  • Antiviral Agents* / pharmacokinetics
  • Antiviral Agents* / pharmacology
  • Gastric Juice* / metabolism
  • Gastric Juice* / virology
  • Herpesvirus 1, Human / growth & development*
  • Humans
  • Intestinal Secretions* / metabolism
  • Intestinal Secretions* / virology
  • Intestine, Small / metabolism
  • Intestine, Small / virology
  • Models, Biological*
  • Stomach / virology
  • Virus Inactivation / drug effects*

Substances

  • Antiviral Agents

Grants and funding

This work has been funded by the University of Messina (Research & Mobility 2015 Project, project code: RES_AND_MOB_2015_DE_LUCA and Research & Mobility 2016 Project, project code: RES_AND_MOB_2016_Sciortino).