<i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches
In the present study, the hexane extract from branches of <i>Drimys brasiliensis</i> (Winteraceae) displayed potent activity against <i>Schistosoma mansoni</i> parasites (100% mortality of the worms at 200 μg/mL). Bioactivity-guided fractionation afforded, in addition to the...
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2025-01-01
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| author | Eric Umehara Rayssa A. Cajas Gabriel B. Conceição Guilherme M. Antar Adriano D. Andricopulo Josué de Moraes João Henrique G. Lago |
| author_facet | Eric Umehara Rayssa A. Cajas Gabriel B. Conceição Guilherme M. Antar Adriano D. Andricopulo Josué de Moraes João Henrique G. Lago |
| author_sort | Eric Umehara |
| collection | DOAJ |
| description | In the present study, the hexane extract from branches of <i>Drimys brasiliensis</i> (Winteraceae) displayed potent activity against <i>Schistosoma mansoni</i> parasites (100% mortality of the worms at 200 μg/mL). Bioactivity-guided fractionation afforded, in addition to the previously reported bioactive sesquiterpene 3,6-epidioxy-bisabola-1,10-diene, two chemically related drimane sesquiterpenes—polygodial (<b>1</b>) and 9-deoxymuzigadial (<b>2</b>). The anti-<i>S. mansoni</i> effects for compounds <b>1</b> and <b>2</b> were determined in vitro, with compound <b>1</b> demonstrating significant potency (EC<sub>50</sub> value of 10 μM for both male and female worms), while <b>2</b> was inactive. Cytotoxicity assays against Vero cells revealed no toxicity for either compound (CC<sub>50</sub> > 200 μM). Additionally, an in silico analysis was conducted using the SwissADME platform for <b>1</b>, revealing that this natural sesquiterpene exhibited adherence to several ADME parameters and no PAINS violations. Finally, in vivo studies with <i>S. mansoni</i>-infected mice treated with compound <b>1</b> demonstrated a 44.0% reduction in worm burden, accompanied by decreases in egg production of 71.8% in feces and 69.5% in intestines. These findings highlight the potential of polygodial (<b>1</b>) as a promising prototype for schistosomiasis treatment. |
| format | Article |
| id | doaj-art-0bc0dd6ed3ba4b91a4da92d8a3300a66 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-0bc0dd6ed3ba4b91a4da92d8a3300a662025-01-24T13:43:20ZengMDPI AGMolecules1420-30492025-01-0130226710.3390/molecules30020267<i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> BranchesEric Umehara0Rayssa A. Cajas1Gabriel B. Conceição2Guilherme M. Antar3Adriano D. Andricopulo4Josué de Moraes5João Henrique G. Lago6Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André 09280-560, SP, BrazilNúcleo de Pesquisas em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, BrazilNúcleo de Pesquisas em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, BrazilDepartamento de Ciências Agrárias e Biológicas, Universidade Federal do Espírito Santo, São Mateus 29932-540, ES, BrazilLaboratório de Química Medicinal e Computacional, Centro de Pesquisa e Inovação em Biodiversidade e Fármacos, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos 13563-120, SP, BrazilNúcleo de Pesquisas em Doenças Negligenciadas, Universidade Guarulhos, Guarulhos 07023-070, SP, BrazilCentro de Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André 09280-560, SP, BrazilIn the present study, the hexane extract from branches of <i>Drimys brasiliensis</i> (Winteraceae) displayed potent activity against <i>Schistosoma mansoni</i> parasites (100% mortality of the worms at 200 μg/mL). Bioactivity-guided fractionation afforded, in addition to the previously reported bioactive sesquiterpene 3,6-epidioxy-bisabola-1,10-diene, two chemically related drimane sesquiterpenes—polygodial (<b>1</b>) and 9-deoxymuzigadial (<b>2</b>). The anti-<i>S. mansoni</i> effects for compounds <b>1</b> and <b>2</b> were determined in vitro, with compound <b>1</b> demonstrating significant potency (EC<sub>50</sub> value of 10 μM for both male and female worms), while <b>2</b> was inactive. Cytotoxicity assays against Vero cells revealed no toxicity for either compound (CC<sub>50</sub> > 200 μM). Additionally, an in silico analysis was conducted using the SwissADME platform for <b>1</b>, revealing that this natural sesquiterpene exhibited adherence to several ADME parameters and no PAINS violations. Finally, in vivo studies with <i>S. mansoni</i>-infected mice treated with compound <b>1</b> demonstrated a 44.0% reduction in worm burden, accompanied by decreases in egg production of 71.8% in feces and 69.5% in intestines. These findings highlight the potential of polygodial (<b>1</b>) as a promising prototype for schistosomiasis treatment.https://www.mdpi.com/1420-3049/30/2/267antischistosomal activitypolygodial9-deoxymuzigadial<i>Drimys brasiliensis</i>schistosomiasis |
| spellingShingle | Eric Umehara Rayssa A. Cajas Gabriel B. Conceição Guilherme M. Antar Adriano D. Andricopulo Josué de Moraes João Henrique G. Lago <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches Molecules antischistosomal activity polygodial 9-deoxymuzigadial <i>Drimys brasiliensis</i> schistosomiasis |
| title | <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches |
| title_full | <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches |
| title_fullStr | <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches |
| title_full_unstemmed | <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches |
| title_short | <i>In Vitro</i> and <i>In Vivo</i> Evaluation of the Antischistosomal Activity of Polygodial and 9-Deoxymuzigadial Isolated from <i>Drimys brasiliensis</i> Branches |
| title_sort | i in vitro i and i in vivo i evaluation of the antischistosomal activity of polygodial and 9 deoxymuzigadial isolated from i drimys brasiliensis i branches |
| topic | antischistosomal activity polygodial 9-deoxymuzigadial <i>Drimys brasiliensis</i> schistosomiasis |
| url | https://www.mdpi.com/1420-3049/30/2/267 |
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