1. Academic Validation
  2. S-Euglobals: biomimetic synthesis, antileishmanial, antimalarial, and antimicrobial activities

S-Euglobals: biomimetic synthesis, antileishmanial, antimalarial, and antimicrobial activities

  • Bioorg Med Chem. 2008 Feb 1;16(3):1328-36. doi: 10.1016/j.bmc.2007.10.055.
Sandip B Bharate 1 Shabana I Khan Babu L Tekwani Melissa Jacob Ikhlas A Khan Inder Pal Singh
Affiliations

Affiliation

  • 1 Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India.
Abstract

Several new euglobal analogues (named as S-euglobals) were synthesized from phloroglucinol via a biomimetic three-component reaction involving Knoevenagel condensation followed by [4+2]-Diels-Alder cycloaddition with monoterpene. Newly synthesized euglobal analogues involve monoterpenes that have not yet been encountered in natural euglobals. S-Euglobals along with previously synthesized robustadial A and B were evaluated for in vitro antileishmanial, antimalarial, antimicrobial, and cytotoxic activities. Out of 16, nine analogues were found to exhibit antileishmanial activity against Leishmania donovani promastigotes. Analogue 7 was the most potent with IC(50) of 2.4 microg/mL and IC(90) of 8 microg/mL, followed by analogues 8 and 11 (IC(50) 5.5 and 9.5 microg/mL). Antileishmanial activity of robustadial A (5) and B (6) was moderate with IC(50) of 20 and 16 microg/mL, respectively. Robustadial A and B and S-euglobal 8 exhibited weak antimalarial activity against Plasmodium falciparum (IC(50) of 2.7-4.76 microg/mL). Few of the euglobal analogues showed Antibacterial activity against methicillin-resistant Staphylococcus aureus. Amongst these, analogue 11 was the most potent with IC(50) of 1.0 microg/mL and MIC of 5.0 microg/mL. Most of the compounds were not cytotoxic up to 25 microg/mL in a panel of cell lines consisting of both Cancer (SK-MEL, KB, BT-549, and SK-OV-3) as well as non-cancer kidney (Vero and LLC-PK11) cells.

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