EDBD—3,6-Epidioxy-1,10-Bisaboladiene—An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection
Abstract
:1. Introduction
2. Results
2.1. Chemical Characterization of EDBD
2.2. EDBD Exhibited Antiparasitic Effects on S. mansoni without Toxicity to Mammalian Cells
2.3. In Silico Evaluation
2.4. In Vivo Evaluation of EDBD—Reduction in Adult Worm Parasite Burden and a Decrease in Egg Production
3. Discussion
4. Materials and Methods
4.1. General Procedures
4.2. Plant Material
4.3. Isolation of EDBD (3,6-Epidioxy-Bisabola-1,10-Diene)
4.4. In Silico Analysis
4.5. Animals, Worms and Cells
4.6. In Vitro Antischistosomal Assay
4.7. Toxicity Profile in Mammalian Cells
4.8. In Vivo Therapeutic Efficacy in an Animal Model of Schistosomiasis
4.9. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | S. mansoni Male EC50/μM | S. mansoni Female EC50/μM | Vero Cell CC50/μM | SI a (Male Worms) | SI a (Female Worms) |
---|---|---|---|---|---|
EDBD | 4.1 ± 1.2 | 4.1 ± 1.2 | ˃200 | ˃48 | ˃48 |
PZQ | 1.1 ± 0.7 | 1.3 ± 0.8 | ˃200 | ˃181 | ˃153 |
Parameters | EDBD | PZQ |
---|---|---|
MW | 236.35 Da | 312.41 Da |
TPSA | 18.46 Å | 40.62 Å |
Log Po/w | 3.79 | 3.00 |
Log S | −3.21 | −3.52 |
Gastroinstestinal absorption | High | High |
BBB | Yes | Yes |
Inhibitor CYP1A2 | No | No |
Inhibitor CYP2C19 | Yes | Yes |
Inhibitor CYP2C9 | Yes | No |
Inhibitor CYP2D6 | No | Yes |
Inhibitor CYP3A4 | No | Yes |
Lipinksi | Yes | Yes |
Ghose | Yes | Yes |
Veber | Yes | Yes |
Egan | Yes | Yes |
Muegge | Yes | Yes |
Bioavaliability Score | 0.55 | 0.55 |
Leadlikeness | Yes | Yes |
PAINS | 0 alert | 0 alert |
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Umehara, E.; Teixeira, T.R.; Cajás, R.A.; Amaro, M.C.; de Moraes, J.; Lago, J.H.G. EDBD—3,6-Epidioxy-1,10-Bisaboladiene—An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection. Antibiotics 2024, 13, 779. https://doi.org/10.3390/antibiotics13080779
Umehara E, Teixeira TR, Cajás RA, Amaro MC, de Moraes J, Lago JHG. EDBD—3,6-Epidioxy-1,10-Bisaboladiene—An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection. Antibiotics. 2024; 13(8):779. https://doi.org/10.3390/antibiotics13080779
Chicago/Turabian StyleUmehara, Eric, Thainá R. Teixeira, Rayssa A. Cajás, Monique C. Amaro, Josué de Moraes, and João Henrique G. Lago. 2024. "EDBD—3,6-Epidioxy-1,10-Bisaboladiene—An Endoperoxide Sesquiterpene Obtained from Drimys brasiliensis (Winteraceae) Exhibited Potent Preclinical Efficacy against Schistosoma mansoni Infection" Antibiotics 13, no. 8: 779. https://doi.org/10.3390/antibiotics13080779