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

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 IC50 of 2.4 mu g/mL and IC90 of 8 mu g/mL, followed by analogues 8 and 11 (IC50 5.5 and 9.5 mu g/mL). Antilelshmanial activity of robustadial A (5) and B (6) was moderate with IC50 of 20 and 16 mu g/mL, respectively. Robustadial A and B and S-euglobal 8 exhibited weak antimalarial activity against Plasmodium falciparum (IC50 of 2.7-4.76 mu g/mL). Few of the eualobal analogues showed antibacterial activity against methicillin-resistant Staphylococcus aureus. Amongst these, analogue I I was the most potent with IC50 of 1.0 mu g/mL and MIC of 5.0 mu g/mL. Most of the compounds were not cytotoxic up to 25 mu g/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. (C) 2007 Elsevier Ltd. All rights reserved.