Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

Matos-Rocha, Thiago José; Lima, Maria do Carmo Alves de; Silva, Anekécia Lauro da; Oliveira, Jamerson Ferreira de; Gouveia, Allana Lemos Andrade; Silva, Vinícius Barros Ribeiro da; Almeida Júnior, Antônio Sérgio Alves de; Brayner, Fábio André; Cardoso, Pablo Ramon Gualberto; Pitta-Galdino, Marina da Rocha; Pitta, Ivan da Rocha; Rêgo, Moacyr Jesus Barreto de Melo; Alves, Luiz Carlos; Pitta, Maira Galdino da Rocha

doi:10.1590/S1678-9946201759008

Acessibilidade / Reportar erro

Brasil

Revista do Instituto de Medicina Tropical de São Paulo

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

ORIGINAL ARTICLE • Rev. Inst. Med. trop. S. Paulo 59 • 2017 • https://doi.org/10.1590/S1678-9946201759008 copy

Synthesis and biological evaluation of novel imidazolidine derivatives as candidates to schistosomicidal agents

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT

Introduction:

Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives.

Material and methods:

We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed.

Results:

LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms.

Conclusion:

The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.

KEYWORDS:
Schistosoma mansoni; Imidazolidines; Ultrastructure

Instituto de Medicina Tropical de São Paulo Av. Dr. Enéas de Carvalho Aguiar, 470, 05403-000 - São Paulo - SP - Brazil, Tel. +55 11 3061-7005 - São Paulo - SP - Brazil
E-mail: revimtsp@usp.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] Correspondence to: Thiago José Matos-Rocha. Universidade Federal de Pernambuco, Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisas em Inovação Terapêutica Suely Galdino. Rua Thereza Amélia s/n, Cidade Universitária, CEP 50670-901, Recife, PE, Brazil. E-mail: thy_rocha@hotmail.com

Groups	Time (h)	Concentration (µM)				Remarks (worms)	Cytotoxicity (µM)^a
		100	40	20	5
		Mortality (%)
RPMI 1640	24	-	-	-	-	Paired worms without apparent morphological change, presence of eggs.	-
	48	-	-	-	-
	72	-	-	-	-
	96	-	-	-	-
	120	-	-	-	-
DMSO 1.6%	24	-	-	-	-	Paired worms without apparent morphological change, presence of eggs.	-
	48	-	-	-	-
	72	-	-	-	-
	96	-	-	-	-
	120	-	-	-	-
PZQ	24	100	100	100	100	Not paired, no sucker adherence, absence of eggs, tegument morphology altered	> 100
	48	100	100	100	100
	72	100	100	100	100
	96	100	100	100	100
	120	100	100	100	100
LPSF/PTS10	24	100	-	-	-	Unpaired, no sucker adherence, absence of eggs, tegument morphology altered	> 100
	48	100	100	-	-
	72	100	100	100	-
	96	100	100	100	-
	120	100	100	100	-
LPSF/PTS23	24	100	100	100	-	Unpaired, no sucker adherence, absence of eggs, tegument morphology altered	> 100
	48	100	100	100	-
	72	100	100	100	-
	96	100	100	100	-
120	100	100	100	25

Groups	Number of worms	Percentage of worms (%) with respect to motility scores after incubation^a
		24 h			48 h			72 h			96 h			120 h
		3.0	1.5	0	3.0	1.5	0	3.0	1.5	0	3.0	1.5	0	3.0	1.5	0
RPMI 1640		100			100			100			100			100
DMSO 1.6%		100			100			100			100			100
PZQ
5 µM	12			100			100			100			100			100
20 µM	12			100			100			100			100			100
40 µM	12			100			100			100			100			100
100 µM	12			100			100			100			100			100
LPSF/PTS10
5 µM	12	100			100			100			100			100
20 µM	12	50	50			25	75			100			100			100
40 µM	12	25	75				100		75	25			100			100
100 µM	12			100			100			100			100			100
LPSF/PTS23
5 µM	12	100			100			100			100			25	50	25
20 µM	12			100			100			100			100			100
40 µM	12			100			100			100			100			100
100 µM	12			100			100			100			100			100