Synthesis and antiplasmodial evaluation of 1H-1,2,3-triazole grafted 4-aminoquinoline-benzoxaborole hybrids and benzoxaborole analogues

Bioorg Chem. 2021 Apr:109:104733. doi: 10.1016/j.bioorg.2021.104733. Epub 2021 Feb 16.

Abstract

A library of 1H-1,2,3-triazole-tethered 4-aminoquinoline-benzoxaborole hybrids as well as aryl substituted benzoxaborole analogues was synthesized and screened for their anti-plasmodial efficacy against both chloroquine-susceptibility 3D7 and chloroquine-resistant W2 strains of P. falciparum. The inclusion of quinoline core among the synthesized analogues resulted in substantial enhancement of anti-plasmodial activities. Further, the spacer of a flexible alkyl chain is marginally preferred over piperazyl-ethyl in inhibiting growth of P. falciparum. The most potent 4-aminoquinoline-benzoxaborole conjugate with ethyl as spacer exhibited IC50 values of 4.15 and 3.78 μM against 3D7 CQ-susceptible and W2 CQ-resistant strains of P. falciparum with lower cross resistance with Chloroquine. There was no difference in anti-plasmodial activities between the CQ-susceptible 3D7 and CQ-resistant W2 strains of P. falciparum for the benzoxaborole derivatives lacking a quinoline core.

Keywords: 1H-1,2,3-Triazole; 4-Aminoquinoline; Anti-plasmodial activity; Benzoxaborole; Cytotoxicity; Suzuki-miyaura reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Dose-Response Relationship, Drug
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Aminoquinolines
  • Antimalarials
  • Boron Compounds
  • Triazoles
  • 4-aminoquinoline