Hapalindoles from the Cyanobacterium Hapalosiphon sp. Inhibit T Cell Proliferation

Author:

Chilczuk Tomasz1,Steinborn Carmen2,Breinlinger Steffen1,Zimmermann-Klemd Amy Marisa2,Huber Roman2,Enke Heike3,Enke Dan3,Niedermeyer Timo Horst Johannes1,Gründemann Carsten2

Affiliation:

1. Department of Pharmaceutical Biology/Pharmacognosy, Institute of Pharmacy, University of Halle-Wittenberg, Halle, Germany

2. Center for Complementary Medicine, Institute for Infection Prevention and Hospital Epidemiology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

3. Cyano Biotech GmbH, Berlin, Germany

Abstract

AbstractNovel 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.

Funder

Deutsche Forschungsgemeinschaft

Software AG Foundation

DAMUS-Donata e.V.

Bundesministerium für Bildung und Forschung

Publisher

Georg Thieme Verlag KG

Subject

Organic Chemistry,Complementary and alternative medicine,Drug Discovery,Pharmaceutical Science,Pharmacology,Molecular Medicine,Analytical Chemistry

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