title: Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells.
abstract: Guarea macrophyllais a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves fromG. macrophyllausing bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3β,25-diol (1), (23S*,24S*)-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2α,3β-diol (3), and isopimara-7,15-dien-3β-ol (4), in which2and3are identified as new derivatives.In vitroassays were conducted to evaluate the cytotoxic activity of compounds1-4against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound1induced cytotoxic effects on tumor cells, with IC50values of 18.3, 52.1, and 58.9 µM against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound1induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway.
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Brazil.|Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo Andre, Brazil.
authors.forename: Geanne Alexandra A
authors.initials: GAA
authors.lastname: Conserva
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia,Universidade Federal de São Paulo, Brazil.
authors.forename: Natalia
authors.initials: N
authors.lastname: Girola
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia,Universidade Federal de São Paulo, Brazil.|Department of Molecular and Clinical Cancer Medicine, University of Liverpool, United Kingdom.
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Figueiredo
authors.affiliation: Laboratório de Imunologia de Tumores, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Azevedo
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, United Kingdom.
authors.forename: Sasha
authors.initials: S
authors.lastname: Mousdell
authors.affiliation: Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sartorelli
authors.affiliation: Instituto de Química, Universidade Federal de Alfenas, Brazil.
authors.forename: Marisi G
authors.initials: MG
authors.lastname: Soares
authors.affiliation: Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, Brazil.
authors.forename: Guilherme M
authors.initials: GM
authors.lastname: Antar
authors.affiliation: Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo Andre, Brazil.
authors.forename: João Henrique G
authors.initials: JHG
authors.lastname: Lago
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy*; D029582:Meliaceae / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D013729:Terpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D010936:Plant Extracts; D013729:Terpenes