In vitro and in vivo efficacies of novel carbazole aminoalcohols in the treatment of cystic echinococcosis

Wang, Weisi; Li, Jun; Yao, Junmin; Li, Shi-Zhu; Zheng, Xiao; Duan, Liping; Zhang, Wenbao

doi:10.1093/jac/dkx250

Cited by 27 publications

(21 citation statements)

References 40 publications

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“…The viability of vesicles was assessed on the basis of structural vesicle integrity, as previously described (32). The viability of PSCs was assessed by motile behavior observation and 0.1% methylene blue staining (33). More than 50 vesicles and 200 PSCs for each treatment group were analyzed, and three independent experiments were performed.…”

Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Efficacies of the EGFR/MEK/ERK Signaling Inhibitors in the Treatment of Alveolar Echinococcosis

Cheng

Tian

et al. 2020

Antimicrob Agents Chemother

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Alveolar echinococcosis (AE), caused by the larval stage of the cestode Echinococcus multilocularis, is a lethal disease in humans. Novel therapeutic options are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. In this study, we assessed the in vitro and in vivo effects of the epidermal growth factor receptor (EGFR)/MEK/extracellular signal-regulated kinase (ERK) signaling inhibitors, including BIBW2992, CI-1033, and U0126, on E. multilocularis. Our data showed that BIBW2992, CI-1033, and U0126 all displayed in vitro effects on the viability of the E. multilocularis metacestode. These inhibitors also showed protoscolicidal activities and caused severe ultrastructural alterations in the parasite. Moreover, BIBW2992 and CI-1033 exhibited potent proapoptotic effects on E. multilocularis metacestodes. Strikingly, a large portion of the apoptotic cells were found to be the germinative cells. In vivo studies showed that BIBW2992 and U0126 significantly reduced parasite burden, and the parasite obtained from BIBW2992-treated mice displayed impaired structural integrity of the germinal layer. In conclusion, these findings demonstrate the potential of EGFR-mediated signaling as a target for the development of novel anti-AE agents. The EGFR inhibitor BIBW2992 represents a promising drug candidate and/or a lead compound for anti-AE chemotherapy.

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Section: Methodsmentioning

confidence: 99%

In Vitro and In Vivo Efficacies of the EGFR/MEK/ERK Signaling Inhibitors in the Treatment of Alveolar Echinococcosis

Cheng

Tian

et al. 2020

Antimicrob Agents Chemother

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“…Lists of those drugs that were tested in vitro and found not suitable for use in humans after being tested in vivo in experimental animals are available in morespecialized reviews (182,213). There is some hope from in vivo experiments with mefloquine (214)(215)(216)(217)(218) and artemisinin (219,220) derivatives, and very recently, derivatives of carbazole aminoalcohols have been shown effective against cysts of E. granulosus both in vitro and in vivo (221). However, none of these compounds have, as yet, been subjected to pilot clinical trials.…”

Section: Treatment Of Aementioning

confidence: 99%

Echinococcosis: Advances in the 21st Century

Wen¹,

Vuitton²,

et al. 2019

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SUMMARY Echinococcosis is a zoonosis caused by cestodes of the genus Echinococcus (family Taeniidae). This serious and near-cosmopolitan disease continues to be a significant public health issue, with western China being the area of highest endemicity for both the cystic (CE) and alveolar (AE) forms of echinococcosis. Considerable advances have been made in the 21st century on the genetics, genomics, and molecular epidemiology of the causative parasites, on diagnostic tools, and on treatment techniques and control strategies, including the development and deployment of vaccines. In terms of surgery, new procedures have superseded traditional techniques, and total cystectomy in CE, ex vivo resection with autotransplantation in AE, and percutaneous and perendoscopic procedures in both diseases have improved treatment efficacy and the quality of life of patients. In this review, we summarize recent progress on the biology, epidemiology, diagnosis, management, control, and prevention of CE and AE. Currently there is no alternative drug to albendazole to treat echinococcosis, and new compounds are required urgently. Recently acquired genomic and proteomic information can provide a platform for improving diagnosis and for finding new drug and vaccine targets, with direct impact in the future on the control of echinococcosis, which continues to be a global challenge.

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“…Mice models play an important role in studies of developmental biology and host specificity in echinococcosis ( Nakaya et al, 2006 ). Recently, mouse models were successfully used for drug screening and development ( Elissondo et al, 2007 ; Wang et al, 2017 ). To increase the success of secondary infection, we developed a method using micro-cysts cultured in vitro to infect mice ( Zhang et al, 2005 ), and obtained more than 70% of cyst recovery from 50 PSC-generated cysts.…”

Section: Introductionmentioning

confidence: 99%

Echinococcus granulosus Infection Results in an Increase in Eisenbergiella and Parabacteroides Genera in the Gut of Mice

et al. 2018

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Cystic echinococcosis (CE) is a chronic infectious disease caused by Echinococcus granulosus. To confirm whether the infection impacts on the gut microbiota, we established a mouse model of E. granulosus infection in this study whereby BALB/c mice were infected with micro-cysts of E. granulosus. After 4 months of infection, fecal samples were collected for high-throughput sequencing of the hypervariable regions of the 16S rRNA gene. Sequence analysis revealed a total of 13,353 operational taxonomic units (OTUs) with only 40.6% of the OTUs having genera reference information and 101 of the OTUs were significantly increased in infected mice. Bioinformatics analysis showed that the common core microbiota were not significantly changed at family level. However, two genera (Eisenbergiella and Parabacteroides) were enriched in the infected mice (PAMOV A < 0.05) at genus level. Functional analysis indicated that seven pathways were altered in the E. granulosus Infection Group compared with the Uninfected Group. Spearman correlation analysis showed strong correlations of IgG, IgG1 and IgG2a with nine major genera. E. granulosus cyst infection may change the gut microbiota which may be associated with metabolic pathways.

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In vitro and in vivo efficacies of novel carbazole aminoalcohols in the treatment of cystic echinococcosis

Abstract: Our study identifies carbazole aminoalcohols as a class of novel anti-CE agents. Compounds 2 and 24 represent promising drug candidates in anti-CE chemotherapy.

Cited by 27 publications

References 40 publications

In Vitro and In Vivo Efficacies of the EGFR/MEK/ERK Signaling Inhibitors in the Treatment of Alveolar Echinococcosis

In Vitro and In Vivo Efficacies of the EGFR/MEK/ERK Signaling Inhibitors in the Treatment of Alveolar Echinococcosis

Echinococcosis: Advances in the 21st Century

Echinococcus granulosus Infection Results in an Increase in Eisenbergiella and Parabacteroides Genera in the Gut of Mice

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