Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans
Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal po...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/10/2281 |
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| author | Mayara dos Santos Maia Joanda Paolla Raimundo e Silva Thaís Amanda de Lima Nunes Julyanne Maria Saraiva de Sousa Gabriela Cristina Soares Rodrigues Alex France Messias Monteiro Josean Fechine Tavares Klinger Antonio da Franca Rodrigues Francisco Jaime B. Mendonça-Junior Luciana Scotti Marcus Tullius Scotti |
| author_facet | Mayara dos Santos Maia Joanda Paolla Raimundo e Silva Thaís Amanda de Lima Nunes Julyanne Maria Saraiva de Sousa Gabriela Cristina Soares Rodrigues Alex France Messias Monteiro Josean Fechine Tavares Klinger Antonio da Franca Rodrigues Francisco Jaime B. Mendonça-Junior Luciana Scotti Marcus Tullius Scotti |
| author_sort | Mayara dos Santos Maia |
| collection | DOAJ |
| description | Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for <i>Leishmania</i> <i>major</i> and <i>L. (Viannia) braziliensis</i>. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against <i>L. major</i> and 21 lignans against <i>L. braziliensis</i>, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species <i>Justicia</i> <i>aequilabris</i> (Nees) Lindau. All of the identified compounds were able to inhibit the growth of <i>L. braziliensis</i> promastigotes, with the most active compound, (<b>159</b>) epipinoresinol-4-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside, presenting an IC<sub>50</sub> value of 5.39 µM and IC<sub>50</sub> value of 36.51 µM for <i>L. major</i>. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis. |
| first_indexed | 2024-03-10T19:52:28Z |
| format | Article |
| id | doaj.art-50b47054f12c41a9b2eda1a0d5745f85 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T19:52:28Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-50b47054f12c41a9b2eda1a0d5745f852023-11-20T00:13:27ZengMDPI AGMolecules1420-30492020-05-012510228110.3390/molecules25102281Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of LignansMayara dos Santos Maia0Joanda Paolla Raimundo e Silva1Thaís Amanda de Lima Nunes2Julyanne Maria Saraiva de Sousa3Gabriela Cristina Soares Rodrigues4Alex France Messias Monteiro5Josean Fechine Tavares6Klinger Antonio da Franca Rodrigues7Francisco Jaime B. Mendonça-Junior8Luciana Scotti9Marcus Tullius Scotti10Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilMulti-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilInfectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, BrazilInfectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, BrazilLaboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilLaboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilMulti-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilInfectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, BrazilLaboratory of Synthesis and Drug Delivery, State University of Paraíba, João Pessoa-PB 58071-160, BrazilLaboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilLaboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, BrazilLeishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for <i>Leishmania</i> <i>major</i> and <i>L. (Viannia) braziliensis</i>. A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against <i>L. major</i> and 21 lignans against <i>L. braziliensis</i>, with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species <i>Justicia</i> <i>aequilabris</i> (Nees) Lindau. All of the identified compounds were able to inhibit the growth of <i>L. braziliensis</i> promastigotes, with the most active compound, (<b>159</b>) epipinoresinol-4-<i>O</i>-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside, presenting an IC<sub>50</sub> value of 5.39 µM and IC<sub>50</sub> value of 36.51 µM for <i>L. major</i>. Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis.https://www.mdpi.com/1420-3049/25/10/2281leishmaniasislignanvirtual screeningmolecular dockingcomputer-aided drug design |
| spellingShingle | Mayara dos Santos Maia Joanda Paolla Raimundo e Silva Thaís Amanda de Lima Nunes Julyanne Maria Saraiva de Sousa Gabriela Cristina Soares Rodrigues Alex France Messias Monteiro Josean Fechine Tavares Klinger Antonio da Franca Rodrigues Francisco Jaime B. Mendonça-Junior Luciana Scotti Marcus Tullius Scotti Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans Molecules leishmaniasis lignan virtual screening molecular docking computer-aided drug design |
| title | Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans |
| title_full | Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans |
| title_fullStr | Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans |
| title_full_unstemmed | Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans |
| title_short | Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans |
| title_sort | virtual screening and the in vitro assessment of the antileishmanial activity of lignans |
| topic | leishmaniasis lignan virtual screening molecular docking computer-aided drug design |
| url | https://www.mdpi.com/1420-3049/25/10/2281 |
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