Natural Compounds Isolated from Stachybotrys chartarum Are Potent Inhibitors of Human Protein Kinase CK2

Samer Haidar,Annika Jagels,Franziska M Jürgens,Joachim Jose,Dagmar Aichele,Hans-Ulrich Humpf

doi:10.3390/molecules26154453

Samer Haidar, Annika Jagels + Show 4 more

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https://doi.org/10.3390/molecules26154453

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Abstract

A large number of secondary metabolites have been isolated from the filamentous fungus Stachybotrys chartarum and have been described before. Fourteen of these natural compounds were evaluated in vitro in the present study for their inhibitory activity towards the cancer target CK2. Among these compounds, stachybotrychromene C, stachybotrydial acetate and acetoxystachybotrydial acetate turned out to be potent inhibitors with IC50 values of 0.32 µM, 0.69 µM and 1.86 µM, respectively. The effects of these three compounds on cell proliferation, growth and viability of MCF7 cells, representing human breast adenocarcinoma as well as A427 (human lung carcinoma) and A431 (human epidermoid carcinoma) cells, were tested using EdU assay, IncuCyte® live-cell imaging and MTT assay. The most active compound in inhibiting MCF7 cell proliferation was acetoxystachybotrydial acetate with an EC50 value of 0.39 µM. In addition, acetoxystachybotrydial acetate turned out to inhibit the growth of all three cell lines completely at a concentration of 1 µM. In contrast, cell viability was impaired only moderately, to 37%, 14% and 23% in MCF7, A427 and A431 cells, respectively.

Highlights

Protein kinase CK2, formerly known as Casein Kinase II, is an enzyme localized in both the cytoplasm and the nucleus of cells and appears to be constitutively active [1].This enzyme is a Ser/Thr kinase, since most if not all of its substrates are phosphorylated at serine or threonine residues [2,3]
Human Protein Kinase CK2 by Natural Compounds from Stachybotrys chartaStachybotrys chartarum rum Fourteen compounds which were isolated from Stachybotrys chartarum as described
These compounds belong to three different scaffolds (Figure 1), namely: stachybotrychromenes A–C, phenylspirodrimanes (stachybotrydial, stachybotrydial acstachybotrychromenes A–C, phenylspirodrimanes and macrocyclic trichothecenes tam acetate, L-671, stachybonoid D, stachybotryamide) and macrocyclic trichothecenes

Summary

Introduction

Protein kinase CK2, formerly known as Casein Kinase II, is an enzyme localized in both the cytoplasm and the nucleus of cells and appears to be constitutively active [1]. This enzyme is a Ser/Thr kinase, since most if not all of its substrates are phosphorylated at serine or threonine residues [2,3]. An overwhelming number of natural products with diverse and complex structures which interact with a variety of biological targets are known [7]. Chemical scaffolds evolved by nature can be optimized in their biological activity with the aim of developing new drugs [7,8]. Newman et al reviewed the use of natural products as a source

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