Triazino indole-quinoline hybrid: a novel approach to antileishmanial agents

Bioorg Med Chem Lett. 2014 Jan 1;24(1):298-301. doi: 10.1016/j.bmcl.2013.11.018. Epub 2013 Nov 17.

Abstract

A novel series of 1,2,4-triazino-[5,6b]indole-3-thione covalently linked to 7-chloro-4-aminoquinoline have been synthesized and evaluated for their in vitro activity against extracellular promastigote and intracellular amastigote form of Leishmania donovani. Among all tested compounds, compounds 7a and 7b were found to be the most active with IC50 values 1.11, 0.36μM and selectivity index (SI) values 67, >1111, respectively, against amastigote form of L. donovani which is several folds more potent than the standard drugs, miltefosine (IC50=8.10μM, SI=7) and sodium stibo-gluconate (IC50=54.60μM, SI⩾7).

Keywords: Antileishmanial; Hybrid; In vitro; Leishmania donovani; Quinoline; Triazino-indole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Leishmania donovani / drug effects*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Structure-Activity Relationship
  • Triazines / chemistry
  • Triazines / pharmacology*

Substances

  • Aminoquinolines
  • Antiprotozoal Agents
  • Indoles
  • Triazines
  • 7-chloro-4-aminoquinoline