Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols

Bioorg Med Chem. 2007 Jan 1;15(1):87-96. doi: 10.1016/j.bmc.2006.10.006. Epub 2006 Oct 10.

Abstract

In the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized O-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. Analogues 12 and 16 exhibited antileishmanial activity against, Leishmania donovani promastigotes with IC(50)s of 5.3 and 4.2microg/mL, respectively. Naturally occurring monomeric formylated acylphloroglucinol compounds, grandinol (2), jensenone (3), and their analogues (29-37), were also synthesized and evaluated for antileishmanial, antimalarial, antibacterial, and antifungal activities. Amongst these, both grandinol and jensenone showed mild to moderate antibacterial, antifungal, and antileishmanial activities. Jensenone (3) was effective against Candida albicans with an IC(50) of 5.5microg/mL but was ineffective against Cryptococcus neoformans and methicillin-resistant Staphylococcus aureus. Among the analogues, 34 was the most active against C. albicans and C. neoformans with IC(50)s of 2.0 and 2.5microg/mL, respectively, and was fungicidal toward Candida albicans.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Candida albicans / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Cryptococcus neoformans / drug effects
  • Epithelial Cells / drug effects
  • Leishmania donovani / drug effects
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / chemistry
  • Phloroglucinol / pharmacology*
  • Staphylococcus aureus / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Anti-Bacterial Agents
  • Antifungal Agents
  • Antiprotozoal Agents
  • Phloroglucinol