Cargando…
Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation
Laying the groundwork on preliminary structure–activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225350/ https://www.ncbi.nlm.nih.gov/pubmed/35736043 http://dx.doi.org/10.3390/jof8060560 |
_version_ | 1784733596979822592 |
---|---|
author | Garcia, Katherine Yasmin M. Quimque, Mark Tristan J. Lambert, Christopher Schmidt, Katharina Primahana, Gian Stradal, Theresia E. B. Ratzenböck, Andreas Dahse, Hans-Martin Phukhamsakda, Chayanard Stadler, Marc Surup, Frank Macabeo, Allan Patrick G. |
author_facet | Garcia, Katherine Yasmin M. Quimque, Mark Tristan J. Lambert, Christopher Schmidt, Katharina Primahana, Gian Stradal, Theresia E. B. Ratzenböck, Andreas Dahse, Hans-Martin Phukhamsakda, Chayanard Stadler, Marc Surup, Frank Macabeo, Allan Patrick G. |
author_sort | Garcia, Katherine Yasmin M. |
collection | PubMed |
description | Laying the groundwork on preliminary structure–activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog triseptatin (1), along with the previously described cytochalasans deoxaphomin B (2) and cytochalasin B (3), and polyketide derivatives cis-4-hydroxy-6-deoxyscytalone (4) and 6-hydroxymellein (5) were isolated from the rice culture of S. triseptata. The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD–TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin. |
format | Online Article Text |
id | pubmed-9225350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92253502022-06-24 Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation Garcia, Katherine Yasmin M. Quimque, Mark Tristan J. Lambert, Christopher Schmidt, Katharina Primahana, Gian Stradal, Theresia E. B. Ratzenböck, Andreas Dahse, Hans-Martin Phukhamsakda, Chayanard Stadler, Marc Surup, Frank Macabeo, Allan Patrick G. J Fungi (Basel) Article Laying the groundwork on preliminary structure–activity relationship study relating to the disruptive activity of cytochalasan derivatives on mammalian cell actin cytoskeleton, we furthered our study on the cytochalasans of the Dothideomycetes fungus, Sparticola triseptata. A new cytochalasan analog triseptatin (1), along with the previously described cytochalasans deoxaphomin B (2) and cytochalasin B (3), and polyketide derivatives cis-4-hydroxy-6-deoxyscytalone (4) and 6-hydroxymellein (5) were isolated from the rice culture of S. triseptata. The structure of 1 was elucidated through NMR spectroscopic analysis and high-resolution mass spectrometry (HR-ESI-MS). The relative and absolute configurations were established through analysis of NOESY spectroscopic data and later correlated with experimental electronic circular dichroism and time-dependent density functional theory (ECD–TDDFT) computational analysis. Compounds 1 and 2 showed cytotoxic activities against seven mammalian cell lines (L929, KB3.1, MCF-7, A549, PC-3, SKOV-3, and A431) and antiproliferative effects against the myeloid leukemia K-562 cancer cell line. Both 1 and 2 were shown to possess properties inhibiting the F-actin network, prompting further hypotheses that should to be tested in the future to enable a well-resolved concept of the structural implications determining the bioactivity of the cytochalasin backbone against F-actin. MDPI 2022-05-25 /pmc/articles/PMC9225350/ /pubmed/35736043 http://dx.doi.org/10.3390/jof8060560 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Garcia, Katherine Yasmin M. Quimque, Mark Tristan J. Lambert, Christopher Schmidt, Katharina Primahana, Gian Stradal, Theresia E. B. Ratzenböck, Andreas Dahse, Hans-Martin Phukhamsakda, Chayanard Stadler, Marc Surup, Frank Macabeo, Allan Patrick G. Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title | Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title_full | Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title_fullStr | Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title_full_unstemmed | Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title_short | Antiproliferative and Cytotoxic Cytochalasins from Sparticola triseptata Inhibit Actin Polymerization and Aggregation |
title_sort | antiproliferative and cytotoxic cytochalasins from sparticola triseptata inhibit actin polymerization and aggregation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225350/ https://www.ncbi.nlm.nih.gov/pubmed/35736043 http://dx.doi.org/10.3390/jof8060560 |
work_keys_str_mv | AT garciakatherineyasminm antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT quimquemarktristanj antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT lambertchristopher antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT schmidtkatharina antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT primahanagian antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT stradaltheresiaeb antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT ratzenbockandreas antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT dahsehansmartin antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT phukhamsakdachayanard antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT stadlermarc antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT surupfrank antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation AT macabeoallanpatrickg antiproliferativeandcytotoxiccytochalasinsfromsparticolatriseptatainhibitactinpolymerizationandaggregation |