Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents
Skin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an inter...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.836572/full |
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| author | Igor V.F. dos Santos Igor V.F. dos Santos Rosivaldo S. Borges Rosivaldo S. Borges Guilherme M. Silva Guilherme M. Silva Lúcio R. de Lima Lúcio R. de Lima Ruan S. Bastos Ruan S. Bastos Ryan S. Ramos Ryan S. Ramos Luciane B. Silva Luciane B. Silva Carlos H. T. P. da Silva Carlos H. T. P. da Silva Cleydson B. R. dos Santos Cleydson B. R. dos Santos Cleydson B. R. dos Santos |
| author_facet | Igor V.F. dos Santos Igor V.F. dos Santos Rosivaldo S. Borges Rosivaldo S. Borges Guilherme M. Silva Guilherme M. Silva Lúcio R. de Lima Lúcio R. de Lima Ruan S. Bastos Ruan S. Bastos Ryan S. Ramos Ryan S. Ramos Luciane B. Silva Luciane B. Silva Carlos H. T. P. da Silva Carlos H. T. P. da Silva Cleydson B. R. dos Santos Cleydson B. R. dos Santos Cleydson B. R. dos Santos |
| author_sort | Igor V.F. dos Santos |
| collection | DOAJ |
| description | Skin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an interesting set of reference compounds due to their in vitro cytotoxic activity with SC cell lines. In view of this, we performed a hierarchical virtual screening study considering Roc-A and its derivatives, with the aim to find new chemical entities with potential activity against SC. For this, we selected 15 molecules (Roc-A and 14 derivatives) and initially used them in docking studies to predict their interactions with Checkpoint kinase 1 (Chk1) as a target for SC. This allowed us to compile and use them as a training set to build robust pharmacophore models, validated by Pearson’s correlation (p) values and hierarchical cluster analysis (HCA), subsequentially submitted to prospective virtual screening using the Molport® database. Outputted compounds were then selected considering their similarities to Roc-A, followed by analyses of predicted toxicity and pharmacokinetic properties as well as of consensus molecular docking using three software. 10 promising compounds were selected and analyzed in terms of their properties and structural features and, also, considering their previous reports in literature. In this way, the 10 promising virtual hits found in this work may represent potential anti-SC agents and further investigations concerning their biological tests shall be conducted. |
| first_indexed | 2024-04-12T14:48:19Z |
| format | Article |
| id | doaj.art-ceba2dfb1eda4294b784bf49e6c08bb4 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-12T14:48:19Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-ceba2dfb1eda4294b784bf49e6c08bb42022-12-22T03:28:34ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-06-01910.3389/fmolb.2022.836572836572Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer AgentsIgor V.F. dos Santos0Igor V.F. dos Santos1Rosivaldo S. Borges2Rosivaldo S. Borges3Guilherme M. Silva4Guilherme M. Silva5Lúcio R. de Lima6Lúcio R. de Lima7Ruan S. Bastos8Ruan S. Bastos9Ryan S. Ramos10Ryan S. Ramos11Luciane B. Silva12Luciane B. Silva13Carlos H. T. P. da Silva14Carlos H. T. P. da Silva15Cleydson B. R. dos Santos16Cleydson B. R. dos Santos17Cleydson B. R. dos Santos18Modeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Pará, Belém, BrazilComputational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, BrazilDepartamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Pará, Belém, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Pará, Belém, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Pará, Belém, BrazilComputational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, BrazilDepartamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Ribeirão Preto, BrazilModeling and Computational Chemistry Laboratory, Federal University of Amapá, Macapá, BrazilGraduate Program in Biotechnology and Biodiversity-Network BIONORTE, Federal University of Amapá, Macapá, BrazilGraduate Program in Medicinal Chemistry and Molecular Modeling, Federal University of Pará, Belém, BrazilSkin Cancer (SC) is among the most common type of cancers worldwide. The search for SC therapeutics using molecular modeling strategies as well as considering natural plant-derived products seems to be a promising strategy. The phytochemical Rocaglamide A (Roc-A) and its derivatives rise as an interesting set of reference compounds due to their in vitro cytotoxic activity with SC cell lines. In view of this, we performed a hierarchical virtual screening study considering Roc-A and its derivatives, with the aim to find new chemical entities with potential activity against SC. For this, we selected 15 molecules (Roc-A and 14 derivatives) and initially used them in docking studies to predict their interactions with Checkpoint kinase 1 (Chk1) as a target for SC. This allowed us to compile and use them as a training set to build robust pharmacophore models, validated by Pearson’s correlation (p) values and hierarchical cluster analysis (HCA), subsequentially submitted to prospective virtual screening using the Molport® database. Outputted compounds were then selected considering their similarities to Roc-A, followed by analyses of predicted toxicity and pharmacokinetic properties as well as of consensus molecular docking using three software. 10 promising compounds were selected and analyzed in terms of their properties and structural features and, also, considering their previous reports in literature. In this way, the 10 promising virtual hits found in this work may represent potential anti-SC agents and further investigations concerning their biological tests shall be conducted.https://www.frontiersin.org/articles/10.3389/fmolb.2022.836572/fullhierarchical virtual screeningrocaglamideskin canceranticancer activitypharmacophore |
| spellingShingle | Igor V.F. dos Santos Igor V.F. dos Santos Rosivaldo S. Borges Rosivaldo S. Borges Guilherme M. Silva Guilherme M. Silva Lúcio R. de Lima Lúcio R. de Lima Ruan S. Bastos Ruan S. Bastos Ryan S. Ramos Ryan S. Ramos Luciane B. Silva Luciane B. Silva Carlos H. T. P. da Silva Carlos H. T. P. da Silva Cleydson B. R. dos Santos Cleydson B. R. dos Santos Cleydson B. R. dos Santos Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents Frontiers in Molecular Biosciences hierarchical virtual screening rocaglamide skin cancer anticancer activity pharmacophore |
| title | Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents |
| title_full | Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents |
| title_fullStr | Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents |
| title_full_unstemmed | Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents |
| title_short | Hierarchical Virtual Screening Based on Rocaglamide Derivatives to Discover New Potential Anti-Skin Cancer Agents |
| title_sort | hierarchical virtual screening based on rocaglamide derivatives to discover new potential anti skin cancer agents |
| topic | hierarchical virtual screening rocaglamide skin cancer anticancer activity pharmacophore |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.836572/full |
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