Novel 12N-substituted matrinanes as potential anti-coxsackievirus agents

Bioorg Med Chem Lett. 2017 Feb 15;27(4):829-833. doi: 10.1016/j.bmcl.2017.01.022. Epub 2017 Jan 10.

Abstract

A series of novel 12N-substituted matrinane derivatives were synthesized and evaluated for their activities against coxsackievirus type B3 (CVB3) taking compound 1 as the lead. SAR analysis indicated that the introduction of a suitable heteroaromatic ring on the 12N-atom might be beneficial for the activity. Among them, compound 8a exhibited the highest potency against all CVB serotypes as well as CVA16 with IC50 values ranging from 2.02μM to 7.41μM, indicating a broad-spectrum anti-coxsackieviruse effect. Furthermore, compound 8a demonstrated a good safety profile in vivo. Thus, we consider 12N-substituted matrinanes to be a promising family of anti-coxsackievirus agents, and compound 8a to be a promising drug candidate in the treatment of various diseases related to coxsackievirus infection.

Keywords: Broad-spectrum; Coxsakievirus; Druglike; Matrinane; Structure–activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry*
  • Alkaloids / pharmacology
  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology
  • Enterovirus / drug effects
  • Enterovirus B, Human / drug effects
  • Lethal Dose 50
  • Mice
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Antiviral Agents
  • sophocarpine