Phloroglucinol derivatives from Hypericum species trigger mitochondria' dysfunction in Leishmania amazonensis

被引:15
作者
Aquistapase Dagnino, Ana Paula [1 ,2 ]
Mesquita, Camila Saporiti [1 ]
Dorneles, Gilson Pires [1 ,2 ]
Nunes Teixeira, Vivian de Oliveira [1 ,2 ]
Correa de Barros, Francisco Maikon [3 ]
Ccana-Ccapatinta, Gari Vidal [3 ]
Fonseca, Simone Goncalves [4 ]
Monteiro, Marta Chagas [5 ]
Rodrigues Junior, Luiz Carlos [1 ]
Peres, Alessandra [1 ,6 ,7 ]
von Poser, Gilsane Lino [3 ]
Torres Romao, Pedro Roosevelt [1 ,2 ,8 ]
机构
[1] UFCSPA, Lab Imunol, Porto Alegre, RS, Brazil
[2] UFCSPA, Programa Posgrad Ciencias Saude, Porto Alegre, RS, Brazil
[3] Univ Fed Rio Grande do Sul, Programa Posgrad Ciencias Farmaceut, Av Ipiranga 2752, BR-90610000 Porto Alegre, RS, Brazil
[4] Univ Fed Goias, Inst Patol Trop & Saude Publ, BR-74605050 Goiania, Go, Brazil
[5] Univ Fed Para UFPA, Inst Ciencias Saude, Programa Posgrad Ciencias Farmaceut, BR-66075110 Belem, Para, Brazil
[6] UFCSPA, Programa Posgrad Ciencias Reabilitacao, Porto Alegre, RS, Brazil
[7] Ctr Univ Metodista IPA, Rua Coronel Joaquim Pedro Salgado 80, BR-90420060 Porto Alegre, RS, Brazil
[8] UFCSPA, Programa Posgrad Biociencias, Porto Alegre, RS, Brazil
关键词
Cariphenone A; Isouliginosin B; Leishmanicidal activity; Reactive oxygen species; Uliginosin B; IN-VITRO; BENZOPHENONE; MEMBRANE; DONOVANI; EXTRACT; PROMASTIGOTES; CYTOTOXICITY; AMASTIGOTES; PENTAMIDINE; INHIBITION;
D O I
10.1017/S0031182018000203
中图分类号
R38 [医学寄生虫学]; Q [生物科学];
学科分类号
07 ; 0710 ; 09 ; 100103 ;
摘要
Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1-3 at concentrations 1-100 mu m for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1-3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 mu m, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Sigma fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (Sigma FIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.
引用
收藏
页码:1199 / 1209
页数:11
相关论文
共 39 条
[1]  
Antonello A. M., 2017, PARASITOLOGY, P1
[2]   Resistance to pentamidine in Leishmania mexicana involves exclusion of the drug from the mitochondrion [J].
Basselin, M ;
Denise, H ;
Coombs, GH ;
Barrett, MP .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (12) :3731-3738
[3]   Benzophenones from Hypericum carinatum [J].
Bernardi, APM ;
Ferraz, ABF ;
Albring, DV ;
Bordignon, SAL ;
Schripsema, J ;
Bridi, R ;
Dutra-Filho, CS ;
Henriques, AT ;
von Poser, GL .
JOURNAL OF NATURAL PRODUCTS, 2005, 68 (05) :784-786
[4]   Quantitative structure-activity relationship study of phloroglucinol-terpene adducts as anti-leishmanial agents [J].
Bharate, Sandip B. ;
Singh, Inder Pal .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (14) :4310-4315
[5]   Effects of (-) mammea A/BB isolated from Calophyllum brasiliense leaves and derivatives on mitochondrial membrane of Leishmania amazonensis [J].
Brenzan, M. A. ;
Santos, A. O. ;
Nakamura, C. V. ;
Dias Filho, B. P. ;
Ueda-Nakamura, T. ;
Young, M. C. M. ;
Correa, A. G. ;
Alvim Junior, J. ;
Morgado-Diaz, J. A. ;
Cortez, D. A. G. .
PHYTOMEDICINE, 2012, 19 (3-4) :223-230
[6]   Anti-Trichomonas vaginalis activity of Hypericum polyanthemum extract obtained by supercritical fluid extraction and isolated compounds [J].
Cargnin, Simone Tasca ;
Vieira, Patricia de Brum ;
Cibulski, Samuel ;
Cassel, Eduardo ;
Figueiro Vargas, Rubem Mario ;
Montanha, Jarbas ;
Roehe, Paulo ;
Tasca, Tiana ;
von Poser, Gilsane Lino .
PARASITOLOGY INTERNATIONAL, 2013, 62 (02) :112-117
[7]   Acylphloroglucinol Derivatives from Hypericum andinum: Antidepressant-like Activity of Andinin A [J].
Ccana-Ccapatinta, Gari V. ;
Stolz, Eveline D. ;
da Costa, Paola F. ;
Rates, Stela M. K. ;
von Poser, Gilsane L. .
JOURNAL OF NATURAL PRODUCTS, 2014, 77 (10) :2321-2325
[8]   Dimeric acylphloroglucinols in Hypericum species from sections Brathys and Trigynobrathys [J].
Ccana-Ccapatinta, Gari Vidal ;
Correa de Barros, Francisco Maikon ;
Bridi, Henrique ;
von Poser, Gilsane Lino .
PHYTOCHEMISTRY REVIEWS, 2015, 14 (01) :25-50
[9]   Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis [J].
Costa Junior, Joaquim S. ;
Cardoso de Almeida, Antonia Amanda ;
Falcao Ferraz, Alexandre de Barros ;
Rossatto, Rassa Rebes ;
Silva, Teresinha G. ;
Silva, Paulo B. N. ;
Militao, Gardenia C. G. ;
das Graas Lopes Cito, Antonia Maria ;
Lopes Resende Santana, Lorena Cito ;
de Amorim Carvalho, Fernando Aecio ;
Freitas, Rivelilson M. .
NATURAL PRODUCT RESEARCH, 2013, 27 (4-5) :470-474
[10]   In vitro biological action of aqueous extract from roots of Physalis angulata against Leishmania (Leishmania) amazonensis [J].
da Silva, Raquel Raick P. ;
da Silva, Bruno J. M. ;
Rodrigues, Ana Paula D. ;
Farias, Luis Henrique S. ;
da Silva, Milton N. ;
Alves, Danila Teresa V. ;
Bastos, Gilmara N. T. ;
do Nascimento, Jose Luiz M. ;
Silva, Edilene O. .
BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2015, 15