Novel derivatives of niclosamide synthesis: Its bioactivity and interaction with Schistosoma japonicum cercariae

Wu, Yongquan; Yang, Tianshe; Li, Xun; Wu, Junchen; Yi, Tao; Li, Fuyou; Huang, Chunhui; Fan, Xiaolin

doi:10.1016/j.dyepig.2010.08.002

Cited by 15 publications

(14 citation statements)

References 22 publications

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“…It exhibited strong to moderate cytotoxicity on several human cell lines (12,13). In the last 2 decades, most of the modifications of niclosamide have focused on improving its solubility by altering formulations (e.g., as wettable powder, suspension concentrate, and polymeric controlled-release formulations) (14)(15)(16)(17) or by linking it with surfactants (e.g., polyethylene glycols [PEGs]) (18)(19)(20)(21). To the best of our knowledge, little effort has been made to reduce its toxicity through structure modification.…”

mentioning

confidence: 99%

Synthesis, Bioactivity Evaluation, and Toxicity Assessment of Novel Salicylanilide Ester Derivatives as Cercaricides against Schistosoma japonicum and Molluscicides against Oncomelania hupensis

Wang

Qin

Zhu

et al. 2016

Antimicrob Agents Chemother

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A series of novel salicylanilide ester derivatives were synthesized, characterized, and evaluated for cercaricidal potential against Schistosoma japonicum and molluscicidal potential against Oncomelania hupensis. Four derivatives exhibited remarkable cercaricidal activity superior to that of niclosamide. Among them, the most active compound, 4-chloro-2-((2-methoxy-4-nitrophenyl)carbamoyl)phenyl 4-methoxybenzoate (compound 4c), showed a marked minimum effective cercaricidal concentration as low as 0.43 M and significant molluscicidal activity, with a 50% lethal concentration (LC 50 ) of 0.206 g/m 2 . Particularly, compound 4c displayed 88-fold decreased fish toxicity on Danio rerio and 44-fold reduced cytotoxicity on human kidney HEK293 cells in comparison with the toxicity of niclosamide. The results indicated that 4c could serve as a promising drug candidate, with environmental safety properties, against Schistosoma japonicum at transmission stages. The preliminary molecular mechanism of target compounds in Schistosoma japonicum cercariae was also investigated. Salicylanilide ester derivatives exhibited an inhibitory effect on nitric oxide synthase (NOS) but no effect on lactate dehydrogenase (LDH) and acetylcholinesterase (AChE), and a strong and significant correlation between NOS inhibitory efficacy and cercaricidal activity was observed. In addition, 4c could downregulate the expression of NOS in a dose-dependent manner. These results suggested that NOS was probably one of the drug targets of salicylanilide esters. S chistosomiasis japonica, caused by infection withSchistosoma japonicum, is recognized as a considerable economic and public health concern in Asia, including China, Indonesia, and the Philippines (1-3). According to estimates, over 58 million people are infected (4). Schistosome infection occurs through contact with water contaminated by cercariae, the free-living stage of the parasite shed from intermediate host Oncomelania snails (5). Although praziquantel is available for treatment, there is the fact that it cannot prevent individuals from reinfection. Repeated and intense exposure to cercariae could lead to an ineffective response of early-stage chronic cases in routine control programs, which would increase the risk of infections progressing to an advanced stage. A successful control program of the disease should be constructed as an integrated control scheme including cercaricidal methods, snail control programs, and chemotherapy.Niclosamide has a long track record as a successful molluscicide against Oncomelania snails (6, 7). Moreover, it is effective for cercaria control both under laboratory conditions and in field experiments (8-10). However, niclosamide has relatively poor solubility in water and is a well-known environmentally hazardous chemical. It has been proved highly toxic to 18 species of fish (11). It exhibited strong to moderate cytotoxicity on several human cell lines (12, 13). In the last 2 decades, most of the modifications of niclosamide have focused on improving its so...

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confidence: 99%

Synthesis, Bioactivity Evaluation, and Toxicity Assessment of Novel Salicylanilide Ester Derivatives as Cercaricides against Schistosoma japonicum and Molluscicides against Oncomelania hupensis

Wang

Qin

Zhu

et al. 2016

Antimicrob Agents Chemother

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“…Research Article N-salicylanilide derivatives such as 4a and 4b had been used in snail control, respectively (Scheme 1). Cercaricidal activities of these compounds were also reported in the previous studies (8)(9)(10)(11). However, these compounds were restricted to kill the cercariae in past decades because of their intrinsic disadvantages including lower solubility, heavy density, and sedimentation.…”

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confidence: 63%

Design, Synthesis, and Cercaricidal Activity of Novel High‐efficient, Low‐toxic Self‐spreading PEG‐N‐salicylanilide Derivatives Against Cercariae Larvae of Schistosome Japonicum Floating on the Water Surface

Guo

Zheng

et al. 2014

Chem Biol Drug Des

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Novel cercaricides of PEG-N-salicylanilide derivatives that could self-spread and float on the water surface were designed and synthesized according to the particular habit of cercariae larvae of Schistosome japonicum. The structures of the cercaricides were characterized by the infrared spectra (IR), magnetic resonance ((1) H NMR), and mass spectrum (MS). The images of the floating cercaricides on the water surface were investigated by the Brewster angle microscopy (BAM). When the cercaricides were dropped on the water surface, they could spread along the air-water interface automatically and form thin membranes floating on the water surface immediately. The lethality rate of cercariae for 5a and 6a was more than 90% in 120 min at a surface concentration of 0.008 mg/cm(2) . The non-ionic surfactant-cercaricides not only showed strong cercaricidal activities against the cercariae larvae but also exhibited low toxicities, which offered an effective and environment-friendly approach for the reduction of population infection rate and the realization of schistosome control.

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“…UCs-Ni with its' biocompatiblity and cell-permeability, had the tendency to label cercariae. We have reported the Anti-cercarial activity of niclosamide and it's derivatives [11]. The interaction between fresh cercariae and UCs-Ni was observed using confocal fluorescence microscopy.…”

Section: Cercaria Imagingmentioning

confidence: 99%

“…Moreover, significant auto-fluorescence from the biological tissues is unavoidable for the conventional downconversion fluorescent materials [10]. All these defects are exposed when utilizing derivatives of niclosamide and praziquantel [11,12] as fluorescent probes to achieve cercaria imaging.…”

Section: Introductionmentioning

confidence: 99%

Novel Upconversion Fluorescent Probe for Schistosoma japonicum Cercariae Imaging

Yue¹,

Xie²,

Chen³

et al. 2015

Med chem

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Novel derivatives of niclosamide synthesis: Its bioactivity and interaction with Schistosoma japonicum cercariae

Cited by 15 publications

References 22 publications

Synthesis, Bioactivity Evaluation, and Toxicity Assessment of Novel Salicylanilide Ester Derivatives as Cercaricides against Schistosoma japonicum and Molluscicides against Oncomelania hupensis

Synthesis, Bioactivity Evaluation, and Toxicity Assessment of Novel Salicylanilide Ester Derivatives as Cercaricides against Schistosoma japonicum and Molluscicides against Oncomelania hupensis

Design, Synthesis, and Cercaricidal Activity of Novel High‐efficient, Low‐toxic Self‐spreading PEG‐N‐salicylanilide Derivatives Against Cercariae Larvae of Schistosome Japonicum Floating on the Water Surface

Novel Upconversion Fluorescent Probe for Schistosoma japonicum Cercariae Imaging

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