title: Antifungal, antiprotozoal, cytotoxic and piscicidal properties of Justicidin B and a new arylnaphthalide lignan from Phyllanthus piscatorum.
abstract: Using activity against Candida albicans as a lead, the bioactivity-guided fractionation of the dichloromethane extract of Phyllanthus piscatorum led to the isolation of the arylnaphthalide lignan justicidin B (1), which was found to be present in high amounts, and a new C-11 hydroxylated derivative that we named piscatorin (2). We provide evidence that justicidin B (1) is the main active principle of P. piscatorum, showing the same biological effects that were found for the raw extracts. Justicidin B inhibited the growth of the pathogenic fungi Aspergillus fumigatus (MIC > or = 1 microg/mL), Aspergillus flavus (MIC > or = 12 microg/mL), and Candida albicans (MIC > or = 4 microg/mL), but was not effective against Cryptococcus neoformans and Blastoschizomyces capitatus. Justicidin B also exhibited strong activity against the trypomastigote form of Trypanosoma brucei rhodesiense (IC50 = 0.2 microg/mL) and moderate activity against Trypanosoma cruzi (IC50 = 2.6 microg/mL). Testing against Plasmodium falciparum showed only weak activity. This is the first report on the in vitro fungicidal and antiprotozoal effects of justicidin B. In addition, both compounds exhibited a non-specific cytotoxicity in neoplastic and primary cell cultures. No antibacterial effects were detected. Both compounds were piscicidal against zebra fish and it is shown for the first time that piscatorin (2) and justicidin B (1) are the piscicidal principles of P. piscatorum, exhibiting a potency that is comparable to rotenone.
authors.affiliation: Department of Chemistry and Applied BioSciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zürich, Switzerland.
authors.forename: Jürg
authors.initials: J
authors.lastname: Gertsch
authors.forename: Rebekka Thöni
authors.initials: RT
authors.lastname: Tobler
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Otto
authors.initials: O
authors.lastname: Sticher
authors.forename: Jörg
authors.initials: J
authors.lastname: Heilmann
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D004148:Dioxolanes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D017705:Lignans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D003904:Mitosporic Fungi / Q000187:drug effects; D029803:Phyllanthus; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010961:Plasmodium / Q000187:drug effects; D051381:Rats; D014345:Trypanosoma / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015027:Zebrafish
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D004148:Dioxolanes; D017705:Lignans; D010936:Plant Extracts; C049719:justicidins