Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma
Black cohosh is a well-established medicinal plant and preparations of its rootstock are used for the treatment of mild climacteric complaints. The compounds considered responsible for the therapeutic effect are triterpene glycosides, characterized by a cycloartane scaffold and a pentose moiety. Bec...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-02-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/4/766 |
| _version_ | 1828412773129781248 |
|---|---|
| author | Karin Jöhrer Hermann Stuppner Richard Greil Serhat Sezai Çiçek |
| author_facet | Karin Jöhrer Hermann Stuppner Richard Greil Serhat Sezai Çiçek |
| author_sort | Karin Jöhrer |
| collection | DOAJ |
| description | Black cohosh is a well-established medicinal plant and preparations of its rootstock are used for the treatment of mild climacteric complaints. The compounds considered responsible for the therapeutic effect are triterpene glycosides, characterized by a cycloartane scaffold and a pentose moiety. Because some of these triterpenoids were found to exhibit relevant cytotoxic effects against human breast cancer cells, we decided to investigate their activity on multiple myeloma cell lines NCI-H929, OPM-2, and U266. In a systematic approach, we initially tested three known cytotoxic compounds of three different triterpenoid types, revealing the cimigenol-type triterpenoid as the most active constituent. In a second round, seven naturally occurring cimigenol derivatives were compared with respect to their sugar moiety and their substitution pattern at position C-25, leading to 25-<i>O</i>-methylcimigenol-3-<i>O</i>-α-L-arabinopyranoside as the most potent candidate. Interestingly, not only the methyl group at position C-25 increased the cytotoxic effect but also the arabinose moiety at position C-3 had an impact on the activity. The variety of cimigenol derivatives, moreover, allowed a detailed discussion of their structure−activity relationships, not only for their effect on multiple myeloma cells but also with regard to previous studies on the cytotoxicity of black cohosh triterpenoids. |
| first_indexed | 2024-12-10T12:55:21Z |
| format | Article |
| id | doaj.art-f271b1b775bb4c97805220dac22e04a4 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-10T12:55:21Z |
| publishDate | 2020-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f271b1b775bb4c97805220dac22e04a42022-12-22T01:48:07ZengMDPI AGMolecules1420-30492020-02-0125476610.3390/molecules25040766molecules25040766Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple MyelomaKarin Jöhrer0Hermann Stuppner1Richard Greil2Serhat Sezai Çiçek3Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, AustriaInstitute of Pharmacy, Pharmacognosy, CMBI, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, AustriaTyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, AustriaDepartment of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, 24118 Kiel, GermanyBlack cohosh is a well-established medicinal plant and preparations of its rootstock are used for the treatment of mild climacteric complaints. The compounds considered responsible for the therapeutic effect are triterpene glycosides, characterized by a cycloartane scaffold and a pentose moiety. Because some of these triterpenoids were found to exhibit relevant cytotoxic effects against human breast cancer cells, we decided to investigate their activity on multiple myeloma cell lines NCI-H929, OPM-2, and U266. In a systematic approach, we initially tested three known cytotoxic compounds of three different triterpenoid types, revealing the cimigenol-type triterpenoid as the most active constituent. In a second round, seven naturally occurring cimigenol derivatives were compared with respect to their sugar moiety and their substitution pattern at position C-25, leading to 25-<i>O</i>-methylcimigenol-3-<i>O</i>-α-L-arabinopyranoside as the most potent candidate. Interestingly, not only the methyl group at position C-25 increased the cytotoxic effect but also the arabinose moiety at position C-3 had an impact on the activity. The variety of cimigenol derivatives, moreover, allowed a detailed discussion of their structure−activity relationships, not only for their effect on multiple myeloma cells but also with regard to previous studies on the cytotoxicity of black cohosh triterpenoids.https://www.mdpi.com/1420-3049/25/4/766cimicifuga racemosaacteinsheng mashengmanolcancertumornatural productcytotoxicityapoptosisstructureactivity relationship |
| spellingShingle | Karin Jöhrer Hermann Stuppner Richard Greil Serhat Sezai Çiçek Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma Molecules cimicifuga racemosa actein sheng ma shengmanol cancer tumor natural product cytotoxicity apoptosis structureactivity relationship |
| title | Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma |
| title_full | Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma |
| title_fullStr | Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma |
| title_full_unstemmed | Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma |
| title_short | Structure-Guided Identification of Black Cohosh (<i>Actaea racemosa</i>) Triterpenoids with In Vitro Activity against Multiple Myeloma |
| title_sort | structure guided identification of black cohosh i actaea racemosa i triterpenoids with in vitro activity against multiple myeloma |
| topic | cimicifuga racemosa actein sheng ma shengmanol cancer tumor natural product cytotoxicity apoptosis structureactivity relationship |
| url | https://www.mdpi.com/1420-3049/25/4/766 |
| work_keys_str_mv | AT karinjohrer structureguidedidentificationofblackcohoshiactaearacemosaitriterpenoidswithinvitroactivityagainstmultiplemyeloma AT hermannstuppner structureguidedidentificationofblackcohoshiactaearacemosaitriterpenoidswithinvitroactivityagainstmultiplemyeloma AT richardgreil structureguidedidentificationofblackcohoshiactaearacemosaitriterpenoidswithinvitroactivityagainstmultiplemyeloma AT serhatsezaicicek structureguidedidentificationofblackcohoshiactaearacemosaitriterpenoidswithinvitroactivityagainstmultiplemyeloma |