ea4d77123c711e19e2fef8994dd1185b plants-14-00954.pdf 014d9f91bcd448c7aae22036f5dad2b26263e6e3 plants-14-00954.pdf ffbc793491244b0a700430e4d1d2390055be153f303be5b43b7eb4fa04f241c6 plants-14-00954.pdf Title: Exploring the Anti-Chagas Activity of Zanthoxylum chiloperone’s Seedlings Through Metabolomics and Protein–Ligand Docking Subject: This publication reports the controlled cultivation of Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) in several growth substrates under controlled greenhouse conditions. This plant is well-known for its anti-Chagas (trypanocidal) activity, related to the presence of several -carboline alkaloids. The metabolomic study of Z. chiloperone seedlings over two years of growth (2018–2020) was performed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC GC-TOFMS). The canthin-6-one alkaloids, canthin-6-one and 5-methoxy-canthin-6-one, were putatively identified in Z. chiloperone extracts. Finally, in vitro and in silico studies of trypanocidal activity were performed, suggesting that canthin-6-one alkaloids could interact with the main pharmacological targets against Trypanosoma cruzi, cruzain protease, dihydroorotate dehydrogenase, lanosterol 14-alpha-demethylase, farnesyl diphosphate, and squalene synthases. Keywords: canthin-6-ones; chagas disease; medicinal plants; natural products; plant metabolomics; Rutaceae Author: Ninfa Vera de Bilbao, Ryland T. Giebelhaus, Ryan P. Dias, Maria Elena Ferreira, Miguel Martínez, Lorea Velasco-Carneros, Seo Lin Nam, A. Paulina de la Mata, Jean-Didier Maréchal, Ahissan Innocent Adou, Gloria Yaluff, Elva Serna, Muriel Sylvestre, Susana Torres, Alicia Schinini, Ricardo Galeano, Alain Fournet, James J. Harynuk and Gerardo Cebrián-Torrejón Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Mar 18 16:48:41 2025 CET ModDate: Tue Mar 18 17:14:05 2025 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 12 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1076868 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CAMXTK+EURM10 Type 1 Builtin yes yes yes 10 0 UVXZEU+VnURWPalladioL Type 1 Custom yes yes yes 15 0 DNRKAG+URWPalladioL-Roma Type 1 Custom yes yes yes 21 0 DECIIM+URWPalladioL-Bold Type 1 Custom yes yes yes 27 0 TTNZRR+URWPalladioL-Ital Type 1 Custom yes yes yes 32 0 XRKCAU+URWPalladioL-BoldItal Type 1 Custom yes yes yes 37 0 HMANZF+CMSY10 Type 1 Builtin yes yes yes 42 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 88 0 BCDLEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 96 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 104 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 112 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 115 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 118 0 JHYTSG+CMR10 Type 1 Builtin yes yes yes 132 0 XIRVNA+EURB10 Type 1 Builtin yes yes yes 140 0 MDIKPC+CMBSY10 Type 1 Builtin yes yes yes 145 0 BCDIEE+PalatinoLinotype-Bold CID TrueType Identity-H yes yes yes 157 0 BCDLEE+PalatinoLinotype-Roman CID TrueType Identity-H yes yes yes 165 0 BCDHEE+PalatinoLinotype-Italic CID TrueType Identity-H yes yes yes 173 0 BCDGEE+PalatinoLinotype-Italic TrueType WinAnsi yes yes no 181 0 BCDEEE+PalatinoLinotype-Bold TrueType WinAnsi yes yes no 184 0 BCDFEE+PalatinoLinotype-Roman TrueType WinAnsi yes yes no 187 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-06-04 02:09:25 CEST RepresentationInformation: plants-14-00954.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-06-03 12:15:38 CEST Size: 1076868 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 342 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Seedling Production Destination: subsection.2.1 Item: Title: Plant Material Destination: subsection.2.2 Item: Title: Extract Preparation Destination: subsection.2.3 Item: Title: Metabolomic Study Destination: subsection.2.4 Children: Item: Title: Derivatization Procedure Destination: subsubsection.2.4.1 Item: Title: GC GC-TOFMS Method Destination: subsubsection.2.4.2 Item: Title: Data Processing and Analysis Destination: subsection.2.5 Item: Title: Biological Assays Destination: subsection.2.6 Children: Item: Title: Cytotoxic Activity Destination: subsubsection.2.6.1 Item: Title: Trypanocidal Activity Destination: subsubsection.2.6.2 Item: Title: Computational Methods Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Seedling Production and Extraction Work Destination: subsection.3.1 Item: Title: Metabolomics Analysis Destination: subsection.3.2 Item: Title: Results of Cytotoxicity and Anti-Trypanosoma cruzi Activity In Vitro Destination: subsection.3.3 Item: Title: Computational Analysis Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Exploring the Anti-Chagas Activity of Zanthoxylum chiloperone’s Seedlings Through Metabolomics and Protein Ligand Docking Author: Ninfa Vera de Bilbao, Ryland T. Giebelhaus, Ryan P. Dias, Maria Elena Ferreira, Miguel Martínez, Lorea Velasco-Carneros, Seo Lin Nam, A. Paulina de la Mata, Jean-Didier Maréchal, Ahissan Innocent Adou, Gloria Yaluff, Elva Serna, Muriel Sylvestre, Susana Torres, Alicia Schinini, Ricardo Galeano, Alain Fournet, James J. Harynuk and Gerardo Cebrián-Torrejón Subject: This publication reports the controlled cultivation of Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) in several growth substrates under controlled greenhouse conditions. This plant is well-known for its anti-Chagas (trypanocidal) activity, related to the presence of several -carboline alkaloids. The metabolomic study of Z. chiloperone seedlings over two years of growth (2018 2020) was performed using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC GC-TOFMS). The canthin-6-one alkaloids, canthin-6-one and 5-methoxy-canthin-6-one, were putatively identified in Z. chiloperone extracts. Finally, in vitro and in silico studies of trypanocidal activity were performed, suggesting that canthin-6-one alkaloids could interact with the main pharmacological targets against Trypanosoma cruzi, cruzain protease, dihydroorotate dehydrogenase, lanosterol 14-alpha-demethylase, farnesyl diphosphate, and squalene synthases. 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