Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia
Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of...
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/14219 |
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| author | Karin Jöhrer Mayra Galarza Pérez Brigitte Kircher Serhat Sezai Çiçek |
| author_facet | Karin Jöhrer Mayra Galarza Pérez Brigitte Kircher Serhat Sezai Çiçek |
| author_sort | Karin Jöhrer |
| collection | DOAJ |
| description | Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives. While diosmetin (<b>6</b>) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin (<b>1</b>) and xanthomicrol (<b>3</b>), were particularly active against AML cells and therefore subsequently investigated for their antiproliferative effects at lower concentrations. At a concentration of 2.5 µM, cirsimaritin (<b>1</b>) reduced proliferation of Molm-13 cells by 72% while xanthomicrol (<b>3</b>) even inhibited proliferation to the extent of 84% of control. In addition, both compounds were identified as potent FLT3 inhibitors and thus display promising lead structures for further drug development. Moreover, our results confirmed the chemopreventive properties of flavonoids in general, and in particular of polymethylated flavones, which have been intensively investigated especially over the last decade. |
| first_indexed | 2024-03-09T18:16:31Z |
| format | Article |
| id | doaj.art-40a8414d08544f6ba612de145855bd99 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:16:31Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-40a8414d08544f6ba612de145855bd992023-11-24T08:40:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221421910.3390/ijms232214219Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid LeukemiaKarin Jöhrer0Mayra Galarza Pérez1Brigitte Kircher2Serhat Sezai Çiçek3Tyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, AustriaDepartment of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, 24118 Kiel, GermanyTyrolean Cancer Research Institute, Innrain 66, 6020 Innsbruck, AustriaDepartment of Pharmaceutical Biology, Kiel University, Gutenbergstraße 76, 24118 Kiel, GermanyPhenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives. While diosmetin (<b>6</b>) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin (<b>1</b>) and xanthomicrol (<b>3</b>), were particularly active against AML cells and therefore subsequently investigated for their antiproliferative effects at lower concentrations. At a concentration of 2.5 µM, cirsimaritin (<b>1</b>) reduced proliferation of Molm-13 cells by 72% while xanthomicrol (<b>3</b>) even inhibited proliferation to the extent of 84% of control. In addition, both compounds were identified as potent FLT3 inhibitors and thus display promising lead structures for further drug development. Moreover, our results confirmed the chemopreventive properties of flavonoids in general, and in particular of polymethylated flavones, which have been intensively investigated especially over the last decade.https://www.mdpi.com/1422-0067/23/22/14219hematologic cancerFLT3 inhibitornatural productcytotoxicityapoptosisstructure-activity relationship |
| spellingShingle | Karin Jöhrer Mayra Galarza Pérez Brigitte Kircher Serhat Sezai Çiçek Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia International Journal of Molecular Sciences hematologic cancer FLT3 inhibitor natural product cytotoxicity apoptosis structure-activity relationship |
| title | Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia |
| title_full | Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia |
| title_fullStr | Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia |
| title_full_unstemmed | Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia |
| title_short | Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from <i>Dracocephalum moldavica</i> and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia |
| title_sort | flavones flavonols lignans and caffeic acid derivatives from i dracocephalum moldavica i and their in vitro effects on multiple myeloma and acute myeloid leukemia |
| topic | hematologic cancer FLT3 inhibitor natural product cytotoxicity apoptosis structure-activity relationship |
| url | https://www.mdpi.com/1422-0067/23/22/14219 |
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