دورية أكاديمية
Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro.
| العنوان: | Schistosomicidal effects of histone acetyltransferase inhibitors against Schistosoma japonicum juveniles and adult worms in vitro. |
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| المؤلفون: | Xu J; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.; 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., Wang JY; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of 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; Jiangsu Institute of Parasitic Diseases, Wuxi City, P. R. China., Xia CM; Department of Parasitology, School of Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou City, P. R. China.; 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. |
| المصدر: | PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Aug 19; Vol. 18 (8), pp. e0012428. Date of Electronic Publication: 2024 Aug 19. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
| مستخلص: | 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. Competing Interests: The authors have declared that no competing interests exist. (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| تواريخ الأحداث: | Date Created: 20240819 Latest Revision: 20240819 |
| رمز التحديث: | 20240820 |
| DOI: | 10.1371/journal.pntd.0012428 |
| PMID: | 39159234 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1935-2735 |
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| DOI: | 10.1371/journal.pntd.0012428 |