title: Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.
abstract: The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2',4'-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4'-dihydroxy-3'-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1-5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6-9.9 μM) and a lower effect against CML cells (IC50 = 27.5-30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound.
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Avda Armada Argentina 3555, X5016DHK Córdoba, Argentina.
authors.forename: Mariana Belén
authors.initials: MB
authors.lastname: Joray
authors.affiliation: CIBICI CONICET and Department of Clinical Biochemistry, Faculty of Chemical Science, National University of Córdoba, Haya de la Torre and Medina Allende, Córdoba, Argentina.
authors.forename: Lucas Daniel
authors.initials: LD
authors.lastname: Trucco
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Avda Armada Argentina 3555, X5016DHK Córdoba, Argentina.
authors.forename: María Laura
authors.initials: ML
authors.lastname: González
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Avda Armada Argentina 3555, X5016DHK Córdoba, Argentina.
authors.forename: Georgina Natalia Díaz
authors.initials: GN
authors.lastname: Napal
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Avda Armada Argentina 3555, X5016DHK Córdoba, Argentina.
authors.forename: Sara María
authors.initials: SM
authors.lastname: Palacios
authors.affiliation: CIBICI CONICET and Department of Clinical Biochemistry, Faculty of Chemical Science, National University of Córdoba, Haya de la Torre and Medina Allende, Córdoba, Argentina.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bocco
authors.affiliation: Fine Chemicals and Natural Products Laboratory, School of Chemistry, Catholic University of Córdoba, Avda Armada Argentina 3555, X5016DHK Córdoba, Argentina.
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Carpinella
references.citation: Leuk Res. 2014 Aug;38(8):983-7
references.pmid: 24996974
references.citation: ScientificWorldJournal. 2012;2012:254929
references.pmid: 22654578
references.citation: Bioorg Med Chem. 2009 Sep 1;17(17):6251-6
references.pmid: 19664930
references.citation: Antimicrob Agents Chemother. 2002 May;46(5):1302-9
references.pmid: 11959560
references.citation: Cancer Res. 1990 Nov 1;50(21):6793-9
references.pmid: 1698543
references.citation: J Nat Prod. 2009 Sep;72(9):1631-6
references.pmid: 19689125
references.citation: BMC Complement Altern Med. 2014 Aug 02;14:280
references.pmid: 25086656
references.citation: East Afr Med J. 2002 Nov;79(11):588-92
references.pmid: 12630492
references.citation: Toxicol In Vitro. 2009 Aug;23(5):906-10
references.pmid: 19457454
references.citation: Chem Biol Interact. 2004 Jun 30;148(1-2):57-67
references.pmid: 15223357
references.citation: Bioorg Med Chem Lett. 2001 Dec 17;11(24):3095-7
references.pmid: 11720850
references.citation: Int J Antimicrob Agents. 2011 Aug;38(2):99-107
references.pmid: 21514796
references.citation: J Ethnopharmacol. 2005 Dec 1;102(3):450-6
references.pmid: 16137849
references.citation: J Nat Prod. 2012 Mar 23;75(3):311-35
references.pmid: 22316239
references.citation: Toxicol In Vitro. 2010 Aug;24(5):1333-7
references.pmid: 20471467
references.citation: J Theor Biol. 2000 Jul 21;205(2):231-40
references.pmid: 10873434
references.citation: Biosci Rep. 2013 Nov 25;33(6):null
references.pmid: 24070327
references.citation: An Acad Bras Cienc. 2008 Sep;80(3):467-76
references.pmid: 18797799
references.citation: Int J Antimicrob Agents. 2011 Feb;37(2):156-61
references.pmid: 21163632
references.citation: Bioorg Med Chem Lett. 2007 Dec 15;17(24):6847-52
references.pmid: 17977727
references.citation: Bioorg Med Chem. 2008 Nov 15;16(22):9790-4
references.pmid: 18951808
references.citation: FASEB J. 2014 Dec;28(12):5262-76
references.pmid: 25212220
references.citation: BMC Complement Altern Med. 2014 Dec 24;14:516
references.pmid: 25539720
references.citation: Biocell. 2004 Apr;28(1):31-4
references.pmid: 15176739
references.citation: J Agric Food Chem. 2011 Nov 9;59(21):11534-42
references.pmid: 21958238
references.citation: Int J Antimicrob Agents. 2005 Nov;26(5):343-56
references.pmid: 16323269
references.citation: Phytomedicine. 2011 Aug 15;18(11):994-7
references.pmid: 21514124
references.citation: Drug Discov Today. 2009 Jun;14(11-12):579-88
references.pmid: 19508920
references.citation: Drug Discov Today. 2000 Jul;5(7):294-300
references.pmid: 10856912
references.citation: Phytochemistry. 2007 Apr;68(7):1068-74
references.pmid: 17331551
references.citation: J Ethnopharmacol. 2005 Aug 22;100(1-2):80-4
references.pmid: 15964727
references.citation: BMC Complement Altern Med. 2014 Sep 19;14:340
references.pmid: 25239700
references.citation: Bioresour Technol. 2009 Jul;100(14):3669-73
references.pmid: 19342224
references.citation: Blood Cells Mol Dis. 2002 Mar-Apr;28(2):160-8
references.pmid: 12064912
references.citation: J Med Chem. 1994 Jul 8;37(14):2185-9
references.pmid: 8035425
references.citation: Bioorg Med Chem. 2008 May 15;16(10):5434-40
references.pmid: 18440233
references.citation: Planta Med. 2011 Jan;77(1):95-100
references.pmid: 20645245
references.citation: J Ethnopharmacol. 2013 Mar 7;146(1):198-204
references.pmid: 23276785
references.citation: Food Chem Toxicol. 2013 May;55:214-21
references.pmid: 23274058