title: Synthesis and biological activity of amino acid derivatives of avarone and its model compound.
abstract: A series of eighteen derivatives of marine sesquiterpene quinone avarone and its model system tert-butylquinone with amino acids has been synthesized by nucleophilic addition of amino acids to the quinones. In vitro cytotoxic activity toward human cancer cell lines (HeLa, A549, Fem-X, K562, MDA-MB-453) and normal MRC-5 cell line was determined. Several compounds showed very strong inhibitory activity with IC50 values less than 10 μM. Avarone derivatives were more active than the corresponding tert-butylquinone derivatives. The results of the cytofluorimetric analysis of cell cycle of HeLa cells showed that apoptosis might be one of possible mechanism of action of these compounds in cancer cells. In order to examine the influence of caspases on cell death, the apoptotic mechanisms induced by the tested compounds were determined using specific caspases 3, 8 and 9 inhibitors. For all compounds antibacterial activities against six strains of Gram-positive and four strains of Gram-negative bacteria were determined, as well as antifungal activity against three fungal species.
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Vilipić
authors.affiliation: Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoševa 12, PO Box 815, 11000 Belgrade, Serbia.
authors.forename: Irena
authors.initials: I
authors.lastname: Novaković
authors.affiliation: Institute of Oncology and Radiology, Pasterova 14, 11000 Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stanojković
authors.affiliation: Institute of Oncology and Radiology, Pasterova 14, 11000 Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matić
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
authors.forename: Dejan
authors.initials: D
authors.lastname: Šegan
authors.affiliation: Institute of Marine Biology-Kotor, University of Montenegro, Dobrota bb, 85330 Kotor, Montenegro.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Kljajić
authors.affiliation: Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia. Electronic address: dsladic@chem.bg.ac.rs.
authors.forename: Dušan
authors.initials: D
authors.lastname: Sladić
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D053138:Cyclohexenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008826:Microbial Sensitivity Tests; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D053138:Cyclohexenes; D011809:Quinones; D012717:Sesquiterpenes; C046374:avarone
keywords: Amino acids; Antimicrobial activity; Apoptosis; Avarone; Caspase; Cytotoxicity