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

Several new S-euglobals were synthesized from suitably substituted phloroglucinol and different monoterpenes via a three-component reaction involving Knoevenagel condensation followed by [4+2] cycloaddition. Out of 16, nine analogues were found to exhibit antileishmanial activity. Robustadials also showed moderate antileishmanial activity and weak antimalarial activity against Plasmodium falciparum. Few analogues also showed antibacterial activity.Figure optionsDownload as PowerPoint slide