title: Antiprotozoal and antimicrobial compounds from the plant pathogen Septoria pistaciarum.
abstract: Four new 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids, 17-hydroxy-N-(O-methyl)septoriamycin A (1), 17-acetoxy-N-(O-methyl)septoriamycin A (2), 13-(S)-hydroxy-N-(O-methyl)septoriamycin A (3), and 13-(R)-hydroxy-N-(O-methyl)septoriamycin A (4), together with the known compounds (+)-cercosporin (5), (+)-14-O-acetylcercosporin (6), (+)-di-O-acetylcercosporin (7), lumichrome, and brassicasterol, were isolated from an ethyl acetate extract of a culture medium of Septoria pistaciarum. Methylation of septoriamycin A (8) with diazomethane yielded three di-O-methyl analogues, two of which existed as mixtures of rotamers. We previously reported antimalarial activity of septoriamycin A. This compound also exhibited significant activity against Leishmania donovani promastigotes. Compounds 5-7 showed moderate in vitro activity against L. donovani promastigotes and chloroquine-sensitive (D6) and -resistant (W2) strains of Plasmodium falciparum, whereas compound 5 was fairly active against methicillin-sensitive and methicillin-resistant strains of Staphylococcus aureus. Compounds 5-7 also displayed moderate phytotoxic activity against both a dicot (lettuce, Lactuca sativa) and a monocot (bentgrass, Agrostis stolonifera) and cytotoxicity against a panel of cell lines.
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi , University, Mississippi 38677, USA.
authors.forename: Mallika
authors.initials: M
authors.lastname: Kumarihamy
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Melissa
authors.initials: M
authors.lastname: Jacob
authors.forename: Babu L
authors.initials: BL
authors.lastname: Tekwani
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Duke
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.forename: N P Dhammika
authors.initials: NP
authors.lastname: Nanayakkara
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000962:Antimalarials / Q000302:isolation & purification / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D041221:Candida glabrata / Q000187:drug effects; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015269:Mycobacterium avium Complex / Q000187:drug effects; D010963:Plasmodium falciparum / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000470:Alkaloids; D000890:Anti-Infective Agents; D000962:Antimalarials; D000981:Antiprotozoal Agents; D002738:Chloroquine