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 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.
Bharate
Sandip B
SB
Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160062, India.
Khan
Shabana I
SI
Tekwani
Babu L
BL
Jacob
Melissa
M
Khan
Ikhlas A
IA
Singh
Inder Pal
IP
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007893:Leishmania donovani / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D015269:Mycobacterium avium Complex / Q000187:drug effects; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000981:Antiprotozoal Agents; D013729:Terpenes; D010696:Phloroglucinol