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Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.
Xu, Jing; Wang, Jing-Yi; Huang, Ping; Liu, Zi-Hao; Wang, Yu-Xin; Zhang, Run-Ze; Ma, Hui-Min; Zhou, Bi-Yue; Ni, Xiao-Yan; Xiong, Chun-Rong; Xia, Chao-Ming.
Afiliación
  • Xu J; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Wang JY; MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Key Laboratory of Pathogen Bioscience and Anti-infective Medicine, Suzhou Medical College, Soochow University, Suzhou City, P. R. China.
  • Huang P; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Liu ZH; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Wang YX; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Zhang RZ; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Ma HM; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Zhou BY; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Ni XY; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Xiong CR; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.
  • Xia CM; Jiangsu Institute of Parasitic Diseases, Wuxi City, P. R. China.
PLoS Negl Trop Dis ; 18(8): e0012428, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39159234
ABSTRACT

BACKGROUND:

Schistosomiasis is a relatively neglected parasitic disease that afflicts more than 250 million people worldwide, for which the control strategy relies mainly on mass treatment with the only available drug, praziquantel (PZQ). This approach is not sustainable and is a priority for developing novel drug candidates for the treatment and control of schistosomiasis. METHODOLOGYS/PRINCIPAL

FINDINGS:

In our previous study, we found that DW-3-15, a kind of PZQ derivative, could significantly downregulate the expression of the histone acetyltransferase of Schistosoma japonicum (SjHAT). In this study, several commercially available HAT inhibitors, A485, C646 and curcumin were screened in vitro to verify their antischistosomal activities against S. japonicum juveniles and adults. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of HAT inhibitors in vitro. Quantitative real-time PCR was employed to detect the mRNA level of SjHAT after treatment with different HAT inhibitors. Our results demonstrated that curcumin was the most effective inhibitor against both juveniles and adults of S. japonicum, and its schistosomicidal effects were time- and dose dependent. However, A485 and C646 had limited antischistosomal activity. Scanning electron microscopy demonstrated that in comparison with DW-3-15, curcumin caused similar tegumental changes in male adult worms. Furthermore, both curcumin and DW-3-15 significantly decreased the SjHAT mRNA level, and curcumin dose-dependently reduced the SjHAT expression level in female, male and juvenile worms.

CONCLUSIONS:

Among the three commercially available HATs, curcumin was the most potent against schistosomes. Both curcumin and our patent compound DW-3-15 markedly downregulated the expression of SjHAT, indicating that SjHAT may be a potential therapeutic target for developing novel antischistosomal drug candidates.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma japonicum / Curcumina / Histona Acetiltransferasas Límite: Animals Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Schistosoma japonicum / Curcumina / Histona Acetiltransferasas Límite: Animals Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos