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Planta Med 2020; 86(02): 96-103
DOI: 10.1055/a-1045-5178
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Hapalindoles from the Cyanobacterium Hapalosiphon sp. Inhibit T Cell Proliferation

Tomasz Chilczuk   *
1   Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, Halle, Germany
,
Carmen Steinborn   *
2   Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Steffen Breinlinger   *
1   Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, Halle, Germany
,
Amy Marisa Zimmermann-Klemd
2   Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Roman Huber
2   Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Heike Enke
3   Cyano Biotech GmbH, Berlin, Germany
,
Dan Enke
3   Cyano Biotech GmbH, Berlin, Germany
,
Timo Horst Johannes Niedermeyer   §
1   Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, Halle, Germany
,
Carsten Gründemann   §
2   Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany
› Author AffiliationsSupported by: Deutsche Forschungsgemeinschaft INST 271/388-1
Supported by: Software AG Foundation
Supported by: DAMUS-Donata e.V.
Supported by: Bundesministerium für Bildung und Forschung ANoBIn-16GW0115
Further Information

Publication History

received 06 June 2019
revised 05 November 2019

accepted 06 November 2019

Publication Date:
27 November 2019 (online)

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Abstract

Novel immunomodulating agents are currently sought after for the treatment of autoimmune diseases and cancers. In this context, a screening campaign of a collection of 575 cyanobacteria extracts for immunomodulatory effects has been conducted. The screening resulted in several active extracts. Here we report the results of subsequent studies on an extract from the cyanobacterium Hapalosiphon sp. CBT1235. We identified 5 hapalindoles as the compounds responsible for the observed immunomodulatory effect. These indole alkaloids are produced by several strains of the cyanobacterial family Hapalosiphonaceae. They are known for their anti-infective, cytotoxic, and other bioactivities. Modulation of the activity of human immune cells has not yet been described. The immunomodulatory activity of the hapalindoles was characterized in vitro using flow cytometry-based measurements of T cell proliferation after carboxyfluorescein diacetate succinimidyl ester staining, and apoptosis and necrosis induction after annexin V/propidium iodide staining. The most potent compound, hapalindole A, reduced T cell proliferation with an IC50 of 1.56 µM, while relevant levels of apoptosis were measurable only at 10-fold higher concentrations. Hapalindole A-formamide and hapalindole J-formamide, isolated for the first time from a natural source, had much lower activity than the nonformylated derivatives while, at the same time, being less selective for antiproliferative over apoptotic effects.

Key words

cyanobacteria - Hapalosiphon - hapalindoles - immune modulation - lymphocytes

* These authors contributed equally to this work.


§ These authors contributed equally to this work.


Supporting Information

    1H, 13C, HSQC, HMBC and NOESY spectra, MS data as well as a chromatogram of the micro-fractionation and the results of the inhibition of T cell proliferation by different Hapalosiphon sp. CBT1235 fractions are available as Supporting Information.

  • Supporting Information
 

  • References

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