Structure-Activity Relationship of Piplartine and Synthetic Analogues against Schistosoma mansoni and Cytotoxicity to Mammalian Cells

被引：16

作者：

Campelo, Yuri ^{[1
,2
,3
]}

Ombredane, Alicia ^{[4
]}

Vasconcelos, Andreanne G. ^{[5
]}

Albuquerque, Lucas ^{[6
]}

Moreira, Daniel C. ^{[5
]}

Placido, Alexandra ^{[7
]}

Rocha, Jefferson ^{[2
]}

Fokoue, Harold Hilarion ^{[8
]}

Yamaguchi, Lydia ^{[9
]}

Mafud, Ana ^{[10
]}

Mascarenhas, Yvonne P. ^{[10
]}

Delerue-Matos, Cristina

Borges, Tatiana

Joanitti, Graziella A.

Arcanjo, Daniel D. R. ^{[11
]}

Kato, Massuo J.

Kuckelhaus, Selma A. S. ^{[5
]}

Silva, Marcos P. N. ^{[9
,12
]}

de Moraes, Josue ^{[12
]}

Leite, Jose Roberto S. A. ^{[1
,5
]}

机构：

[1] Univ Fed Piaui, Nucleo Pesquisa Biodiversidade & Biotecnol, Biotec, UFPI, BR-64202020 Parnaiba, PI, Brazil

[2] Ponto Focal Univ Fed Piaui, Programa Posgrad Biotecnol, RENORBIO, UFPI, BR-64049550 Teresina, PI, Brazil

[3] FAHESP, IESVAP, BR-64212790 Parnaiba, PI, Brazil

[4] Univ Brasilia, UnB, Inst Biol, Lab Nanobiotecnol, Campus Darcy Ribeiro, BR-70910900 Brasilia, DF, Brazil

[5] Univ Brasilia, Area Morfol, Fac Med, UnB, BR-70910900 Brasilia, DF, Brazil

[6] Univ Brasilia, Lab Imunol, Fac Med, UnB, BR-70910900 Brasilia, DF, Brazil

[7] ISEP, GRAQ, LAQV REQUIMTE, P-4200072 Porto, Portugal

[8] Univ Fed Rio de Janeiro, CCS, Lab Avaliacao & Sintese Subst Bioat, Cidade Univ, BR-21941902 Rio De Janeiro, RJ, Brazil

[9] Univ Sao Paulo, Inst Quim, BR-01005010 Sao Paulo, SP, Brazil

[10] Univ Sao Paulo, Inst Fis Sao Carlos, BR-01005010 Sao Paulo, SP, Brazil

[11] Univ Fed Piaui, UFPI, NPPM, BR-64202020 Parnaiba, PI, Brazil

[12] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, BR-07023070 Guarulhos, SP, Brazil

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2018年 / 19卷 / 06期

基金：

巴西圣保罗研究基金会;

关键词：

piplartine; analogues; Schistosoma mansoni; cytotoxicity; ANTISCHISTOSOMAL ACTIVITY; ANTIPARASITIC ACTIVITY; ANTIBACTERIAL; PRAZIQUANTEL; AGENTS; DEATH;

D O I：

10.3390/ijms19061802

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is an infectious disease mainly associated with poverty that affects millions of people worldwide. Since treatment for this disease relies only on the use of praziquantel, there is an urgent need to identify new antischistosomal drugs. Piplartine is an amide alkaloid found in several Piper species (Piperaceae) that exhibits antischistosomal properties. The aim of this study was to evaluate the structure-function relationship between piplartine and its five synthetic analogues (19A, 1G, 1M, 14B and 6B) against Schistosoma mansoni adult worms, as well as its cytotoxicity to mammalian cells using murine fibroblast (NIH-3T3) and BALB/cN macrophage (J774A.1) cell lines. In addition, density functional theory calculations and in silico analysis were used to predict physicochemical and toxicity parameters. Bioassays revealed that piplartine is active against S. mansoni at low concentrations (5-10 mu M), but its analogues did not. In contrast, based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays, piplartine exhibited toxicity in mammalian cells at 785 mu M, while its analogues 19A and 6B did not reduce cell viability at the same concentrations. This study demonstrated that piplartine analogues showed less activity against S. mansoni but presented lower toxicity than piplartine.

引用

页数：17

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