title: Antimicrobial and Cytotoxic Activity of Extracts of Ferula heuffelii Griseb. ex Heuff. and Its Metabolites.
abstract: The antimicrobial and cytotoxic activities of isolates (CHCl3 and MeOH extracts and selected metabolites) obtained from the underground parts of the Balkan endemic plant Ferula heuffelii Griseb. ex Heuff. were assessed. The CHCl3 and MeOH extracts exhibited moderate antimicrobial activity, being more pronounced against Gram-positive than Gram-negative bacteria, especially against Staphylococcus aureus (MIC=12.5 μg/ml for both extracts) and Micrococcus luteus (MIC=50 and 12.5 μg/ml, resp.). Among the tested metabolites, (6E)-1-(2,4-dihydroxyphenyl)-3,7,11-trimethyl-3-vinyldodeca-6,10-dien-1-one (2) and (2S*,3R*)-2-[(3E)-4,8-dimethylnona-3,7-dien-1-yl]-2,3-dihydro-7-hydroxy-2,3-dimethylfuro[3,2-c]coumarin (4) demonstrated the best antimicrobial activity. Compounds 2 and 4 both strongly inhibited the growth of M. luteus (MIC=11.2 and 5.2 μM, resp.) and Staphylococcus epidermidis (MIC=22.5 and 10.5 μM, resp.) and compound 2 additionally also the growth of Bacillus subtilis (MIC=11.2 μM). The cytotoxic activity of the isolates was tested against three human cancer cell lines, viz., cervical adenocarcinoma (HeLa), chronic myelogenous leukemia (K562), and breast cancer (MCF-7) cells. The CHCl3 extract exhibited strong cytotoxic activity against all cell lines (IC50 <11.0 μg/ml). All compounds strongly inhibited the growth of the K562 and HeLa cell lines. Compound 4 exhibited also a strong activity against the MCF-7 cell line, comparable to that of cisplatin (IC50 =22.32±1.32 vs. 18.67±0.75μM).
authors.affiliation: University of Belgrade -  Faculty of Pharmacy, Department of Pharmacognosy, Vojvode Stepe 450, RS-11221 Belgrade, (phone: +381-11-3951322; fax: +381-11-3972840).
authors.forename: Ivan
authors.initials: I
authors.lastname: Pavlović
authors.affiliation: University of Belgrade -  Faculty of Pharmacy, Department of Pharmacognosy, Vojvode Stepe 450, RS-11221 Belgrade, (phone: +381-11-3951322; fax: +381-11-3972840). silvana.petrovic@pharmacy.bg.ac.rs.
authors.forename: Silvana
authors.initials: S
authors.lastname: Petrović
authors.affiliation: University of Belgrade -  Faculty of Pharmacy, Department of Microbiology and Immunology, Vojvode Stepe 450, RS-11221 Belgrade.
authors.forename: Marina
authors.initials: M
authors.lastname: Milenković
authors.affiliation: Institute of Oncology and Radiology of Serbia, Pasterova 14, RS-11000, Belgrade.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stanojković
authors.affiliation: University of Illinois, College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, Chicago, IL 60612, USA.
authors.forename: Dejan
authors.initials: D
authors.lastname: Nikolić
authors.affiliation: University of Illinois, College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, Chicago, IL 60612, USA.
authors.forename: Aleksej
authors.initials: A
authors.lastname: Krunić
authors.affiliation: Natural History Museum, Njegoševa 51, RS-11000 Belgrade.
authors.forename: Marjan
authors.initials: M
authors.lastname: Niketić
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005309:Ferula / Q000737:chemistry* / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts
keywords: Antimicrobial activity; CHCl3 Extract; Cytotoxic activity; Ferula heuffelii; MeOH Extract; Prenyl-benzoyl-type sesquiterpenoids; Prenyl-furocoumarin-type sesquiterpenoids; Underground parts