Planta Med 2021; 87(15): 1301
DOI: 10.1055/s-0041-1736947
Abstracts
8. Poster Contributions
8.9 Recent Advances in Medicinal Plant and Natural Product Research

Benzylated dihydrochalcone MF-15 as a potent multitarget inhibitor of cancer cell growth

Temml 1
P Huber-Cantonati
2   Institute of Pharmacy/Pharmaceutical Biology and Clinical Pharmacy, Paracelsus Medical University, Salzburg
,
T Mähr
2   Institute of Pharmacy/Pharmaceutical Biology and Clinical Pharmacy, Paracelsus Medical University, Salzburg
,
F Schwitzer
2   Institute of Pharmacy/Pharmaceutical Biology and Clinical Pharmacy, Paracelsus Medical University, Salzburg
,
C Kretzer
3   Institute of Pharmacy/Pharmaceutical Chemistry, University of Jena
,
A Koeberle
4   Michael Popp Institute, University of Innsbruck
,
F Mayr
1   Institute of Pharmacy/Pharmaceutical and Medicinal Chemistry, Paracelsus Medical University, Salzburg
,
N Engels
5   Institute of Pharmacy/Pharmacognosy, University of Innsbruck.
,
B Waltenberger
5   Institute of Pharmacy/Pharmacognosy, University of Innsbruck.
,
H Stuppner
5   Institute of Pharmacy/Pharmacognosy, University of Innsbruck.
,
O Werz
3   Institute of Pharmacy/Pharmaceutical Chemistry, University of Jena
,
J Pachmayr
2   Institute of Pharmacy/Pharmaceutical Biology and Clinical Pharmacy, Paracelsus Medical University, Salzburg
,
D Schuster
1   Institute of Pharmacy/Pharmaceutical and Medicinal Chemistry, Paracelsus Medical University, Salzburg
› Author Affiliations
V.T. Is funded by the Austrian Science Fund (FWF) projectT942
 

Dihydrochalcones constitute a family of natural flavonoids that are well known for their anti-oxidative abilities. We investigated MF-15, a benzylated dihydrochalcone found in Melodorum fruticosum in an in silico profiling approach and discovered that this natural product possesses a wide array of bioactivities that also translate into anti-proliferation activity on different cancer cell lines. MF-15 was shown to inhibit 17β-​hydroxysteroid dehydrogenase type 5 (87% inhibition at a concentration of 10 µM) [1] and also to inhibit microsomal prostaglandin E synthase 1 with an IC50 of 1.8 µM. A Lipid mediator profiling in activated macrophages displayed a strong potential for upregulating of resolvins that resolve inflammation. In addition, we also confirmed inhibition of the androgen receptor by MF-15. These individual activities lead to a dose dependent inhibition of cell proliferation in castration resistant prostate cancer cell lines [1] as well as liver (Hep3B, IC50 of 6.38 µM) and thyroid cancer cell lines (TPC1,IC50 of 10.45 µM). In silico analysis of the binding modes of this compound interacting with different target proteins suggests that structural optimization towards higher bioactivity and selectivity is feasible. MF-15’s impressive polypharmacological profile with the dual anti-androgenic effect, in combination with its anti-inflammatory properties render it an extraordinary lead structure from the class of dihydrochalcones.



Publication History

Article published online:
13 December 2021

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  • References

  • 1 Kafka et al Cancers 12(8):2092. doi: 10.3390/cancers12082092.