title: Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.
abstract: In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar, Punjab 160062, India.
authors.forename: Sandip B
authors.initials: SB
authors.lastname: Bharate
authors.forename: Kamlesh K
authors.initials: KK
authors.lastname: Bhutani
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Inder Pal
authors.initials: IP
authors.lastname: Singh
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D032701:Biomimetics; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology; D007893:Leishmania donovani / Q000187:drug effects*; D021261:Parasitic Sensitivity Tests; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D000981:Antiprotozoal Agents; D013729:Terpenes; C065476:euglobal G2; C065475:euglobal G3; C065477:euglobal G1; D010696:Phloroglucinol