Abstract
Schistosomiasis is one of the world’s major public health problems, and praziquantel is the only available drug to treat this notable neglected disease. Drug combinations have been considered an important strategy for treatment of infectious diseases, which might enhance therapeutic efficacy and delaying resistance. In this study, we have examined the in vitro activities of the amide piplartine and the antimicrobial peptide dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including 3-hour-old and 7-day-old schistosomula and 49-day-old adult schistosomes as well as on egg output by adult worms. We calculated the median lethal concentrations (LC50) of 7.87 and 17.99 μM on 49-day-old adults, 11.02 and 71.58 μM on 7-day-old schistosomula, and 70.87 and 98.42 μM on 3-hour-old schistosomula for piplartine and dermaseptin, respectively. Most Piplartine/dermaseptin combinations showed synergistic effect, with combination index (CI) values less than 0.9 when S. mansoni adults or schistosomula were simultaneously incubated with both drugs in vitro; synergy between these two compounds was also indicated using isobolograms. Additionally, we observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy. Furthermore, egg laying of surviving worms was considerably more reduced when exposed to the piplartine/dermaseptin combinations than each drug alone, and this inhibition was irreversible. This is the first report on the synergistic effect between piplartine and dermaseptin against S. mansoni and opens the route to further studies (e.g. in vivo) to characterize this combination in greater detail.
Keywords: Schistosoma mansoni, piplartine, dermaseptin, schistosomiasis, schistosomicidal activity, combination chemotherapy, synergism, combination index, anthelmintic activity, parasitic disease, natural compounds, confocal laser scanning microscopy, helminth
Current Medicinal Chemistry
Title:In Vitro Synergistic Interaction Between Amide Piplartine and Antimicrobial Peptide Dermaseptin Against Schistosoma mansoni Schistosomula and Adult Worms
Volume: 20 Issue: 2
Author(s): J. de Moraes, J. Keiser, K. Ingram, C. Nascimento, L.F. Yamaguchi, C.R. Bittencourt, M.P. Bemquerer, J.R. Leite, M.J. Kato and E. Nakano
Affiliation:
Keywords: Schistosoma mansoni, piplartine, dermaseptin, schistosomiasis, schistosomicidal activity, combination chemotherapy, synergism, combination index, anthelmintic activity, parasitic disease, natural compounds, confocal laser scanning microscopy, helminth
Abstract: Schistosomiasis is one of the world’s major public health problems, and praziquantel is the only available drug to treat this notable neglected disease. Drug combinations have been considered an important strategy for treatment of infectious diseases, which might enhance therapeutic efficacy and delaying resistance. In this study, we have examined the in vitro activities of the amide piplartine and the antimicrobial peptide dermaseptin 01 administered singly or in combination against Schistosoma mansoni of different ages including 3-hour-old and 7-day-old schistosomula and 49-day-old adult schistosomes as well as on egg output by adult worms. We calculated the median lethal concentrations (LC50) of 7.87 and 17.99 μM on 49-day-old adults, 11.02 and 71.58 μM on 7-day-old schistosomula, and 70.87 and 98.42 μM on 3-hour-old schistosomula for piplartine and dermaseptin, respectively. Most Piplartine/dermaseptin combinations showed synergistic effect, with combination index (CI) values less than 0.9 when S. mansoni adults or schistosomula were simultaneously incubated with both drugs in vitro; synergy between these two compounds was also indicated using isobolograms. Additionally, we observed alterations on the tegumental surface of schistosomula and adult schistosomes by means of laser scanning confocal microscopy. Furthermore, egg laying of surviving worms was considerably more reduced when exposed to the piplartine/dermaseptin combinations than each drug alone, and this inhibition was irreversible. This is the first report on the synergistic effect between piplartine and dermaseptin against S. mansoni and opens the route to further studies (e.g. in vivo) to characterize this combination in greater detail.
Export Options
About this article
Cite this article as:
de Moraes J., Keiser J., Ingram K., Nascimento C., Yamaguchi L.F., Bittencourt C.R., Bemquerer M.P., Leite J.R., Kato M.J. and Nakano E., In Vitro Synergistic Interaction Between Amide Piplartine and Antimicrobial Peptide Dermaseptin Against Schistosoma mansoni Schistosomula and Adult Worms, Current Medicinal Chemistry 2013; 20 (2) . https://dx.doi.org/10.2174/0929867311320020010
DOI https://dx.doi.org/10.2174/0929867311320020010 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry The Recent Progresses on The Improved Therapy of Melanoma by Novel Drug Delivery Systems
Current Drug Targets PET and SPECT Imaging for the Acceleration of Anti-Cancer Drug Development
Current Drug Targets The Pharmacogenomics “Side-effect” of TP53/EGFR in Non-small Cell Lung Cancer Accompanied with Atorvastatin Therapy: A Functional Network Analysis
Anti-Cancer Agents in Medicinal Chemistry Regulation of the Urokinase Receptor (uPAR) by LDL Receptor-related Protein-1 (LRP1)
Current Pharmaceutical Design Epidemiology of Upper Gastrointestinal Damage Associated with Low-Dose Aspirin
Current Pharmaceutical Design New 1-phthalazinone Scaffold based Compounds: Design, Synthesis, Cytotoxicity and Protein Kinase Inhibition Activity
Mini-Reviews in Medicinal Chemistry Evaluation of Cell-detaching Effect of EDTA in Combination with Oxaliplatin for a Possible Application in HIPEC After Cytoreductive Surgery: A Preliminary in-vitro Study
Current Pharmaceutical Design Review of Synthesis, Biological Assay and QSAR Studies of β-Secretase Inhibitors
Current Computer-Aided Drug Design Prostate Cancer Prevention in the Developing World - What are we Waiting for?
Current Pharmacogenomics and Personalized Medicine Anticancer Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibitors: Current Status, Challenges and Future Prospects in Management of Epilepsy
CNS & Neurological Disorders - Drug Targets Recent Patents Relating to Tumor Suppressor Genes
Recent Patents on DNA & Gene Sequences Using Compound Similarity and Functional Domain Composition for Prediction of Drug-Target Interaction Networks
Medicinal Chemistry Evolution of Novel Non-Steroidal Anti-Inflammatory Drugs with Reduced Gastrointestinal Adverse Effects
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Immunoglobulin G Expression and its Potential Role in Primary and Metastatic Breast Cancers
Current Molecular Medicine The Application of the RNA Interference Technologies for KRAS: Current Status, Future Perspective and Associated Challenges
Current Topics in Medicinal Chemistry ZD6474, a Small Molecule Tyrosine Kinase Inhibitor, Potentiates the Anti-Tumor and Anti-Metastasis Effects of Radiation for Human Nasopharyngeal Carcinoma
Current Cancer Drug Targets Microspheres and Microcapsules for Protein Delivery: Strategies of Drug Activity Retention
Current Pharmaceutical Design Anti-Vascular Endothelial Growth Factor (VEGF) Therapy: A New Cause of Hypertension
Current Hypertension Reviews New Medical Strategies for Midgut Carcinoids
Anti-Cancer Agents in Medicinal Chemistry