*Article* **Flavones, Flavonols, Lignans, and Caffeic Acid Derivatives from** *Dracocephalum moldavica* **and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia**

**Karin Jöhrer 1, Mayra Galarza Pérez 2, Brigitte Kircher 1,3 and Serhat Sezai Çiçek 2,\***


**Abstract:** 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 (**6**) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin (**1**) and xanthomicrol (**3**), 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 (**1**) reduced proliferation of Molm-13 cells by 72% while xanthomicrol (**3**) 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.

**Keywords:** hematologic cancer; FLT3 inhibitor; natural product; cytotoxicity; apoptosis; structure-activity relationship; apigenin; luteolin; quercetin; kaempferol
