Planta Med 2017; 83(16): 1289-1296
DOI: 10.1055/s-0043-107241
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Terpenoids from Leaves of Guarea macrophylla Display In Vitro Cytotoxic Activity and Induce Apoptosis In Melanoma Cells

Geanne Alexandra A. Conserva1, 2, Natalia Girola3, Carlos R. Figueiredo3, 4, Ricardo A. Azevedo5, Sasha Mousdell4, Patricia Sartorelli1, Marisi G. Soares6, Guilherme M. Antar7, João Henrique G. Lago2
  • 1Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Brazil
  • 2Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo Andre, Brazil
  • 3Departamento de Microbiologia, Imunologia e Parasitologia,Universidade Federal de São Paulo, Brazil
  • 4Department of Molecular and Clinical Cancer Medicine, University of Liverpool, United Kingdom
  • 5Laboratório de Imunologia de Tumores, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil
  • 6Instituto de Química, Universidade Federal de Alfenas, Brazil
  • 7Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, Brazil
Further Information

Publication History

received 12 November 2016
revised 07 February 2017

accepted 20 March 2017

Publication Date:
10 April 2017 (eFirst)


Guarea macrophylla is 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 from G. macrophylla using 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 which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 14 against 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 compound 1 induced cytotoxic effects on tumor cells, with IC50 values 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 compound 1 induced 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.

Supporting information