title: Sorbicillinoid analogs with cytotoxic and selective anti-Aspergillus activities from Scytalidium album.
abstract: As part of an ongoing project to explore filamentous fungi for anticancer and antibiotic leads, 11 compounds were isolated and identified from an organic extract of the fungus Scytalidium album (MSX51631) using bioactivity-directed fractionation against human cancer cell lines. Of these, eight compounds were a series of sorbicillinoid analogs (1-8), of which four were new (scalbucillin A (2), scalbucillin B (3), scalbucillin C (6) and scalbucillin D (8)), two were phthalides (9-10) and one was naphthalenone (11). Compounds (1-11) were tested in the MDA-MB-435 (melanoma) and SW-620 (colon) cancer cell lines. Compound 1 was the most potent with IC50 values of 1.5 and 0.5 μM, followed by compound 5 with IC50 values of 2.3 and 2.5 μM at 72 h. Compound 1 showed a 48-h IC50 value of 3.1 μM when tested against the lymphocytic leukemia cell line OSU-CLL, while the nearly identical compound 5 had almost no activity in this assay. Compounds 1 and 5 showed selective and equipotent activity against Aspergillus niger with minimum IC values of 0.05 and 0.04 μg ml(-1) (0.20 and 0.16 μM), respectively. The in vitro hemolytic activity against sheep erythrocytes of compounds 1 and 5 was investigated and were found to provoke 10% hemolysis at 52.5 and 45.0 μg ml(-1), respectively, indicative of a promising safety factor.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Tamam
authors.initials: T
authors.lastname: El-Elimat
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Huzefa A
authors.initials: HA
authors.lastname: Raja
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Figueroa
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Swanson
authors.affiliation: Department of Biological Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Falkinham
authors.affiliation: 1] Division of Hematology, College of Medicine, The Ohio State University, Columbus, OH, USA [2] Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Lucas
authors.affiliation: Division of Hematology, College of Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Grever
authors.affiliation: Natural Products Laboratory, Research Triangle Institute, Research Triangle Park, NC, USA.
authors.forename: Mansukh C
authors.initials: MC
authors.lastname: Wani
authors.affiliation: Mycosynthetix Inc., Hillsborough, NC, USA.
authors.forename: Cedric J
authors.initials: CJ
authors.lastname: Pearce
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC, USA.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Oberlies
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001230:Aspergillus / Q000187:drug effects*; D045744:Cell Line, Tumor; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D003904:Mitosporic Fungi / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents