Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues

Bioorg Med Chem. 2006 Mar 15;14(6):1750-60. doi: 10.1016/j.bmc.2005.10.027. Epub 2005 Nov 7.

Abstract

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / chemical synthesis
  • Anti-Infective Agents / chemistry*
  • Anti-Infective Agents / pharmacology
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology
  • Biomimetics*
  • Cells, Cultured
  • Fibroblasts / drug effects
  • Humans
  • Kidney / cytology
  • Leishmania donovani / drug effects*
  • Parasitic Sensitivity Tests
  • Phloroglucinol / analogs & derivatives
  • Phloroglucinol / chemical synthesis
  • Phloroglucinol / chemistry*
  • Phloroglucinol / pharmacology
  • Terpenes / chemical synthesis
  • Terpenes / chemistry
  • Terpenes / pharmacology

Substances

  • Anti-Infective Agents
  • Antimalarials
  • Antiprotozoal Agents
  • Terpenes
  • euglobal G2
  • euglobal G3
  • euglobal G1
  • Phloroglucinol