Synthesis of usnic acid derivatives and evaluation of their antiproliferative activity against cancer cells

Agnieszka Pyrczak-Felczykowska , Rajeshwar Narlawar , Anna Pawlik , Beata Guzow-Krzemińska , Damian Artymiuk , Aleksandra Hać , Kamil Ryś , Louis M. Rendina , Tristan A. Reekie , Anna Herman-Antosiewicz , Michael Kassiou

Abstract

Usnic acid is a secondary metabolite abundantly found in lichens, for which promising cytotoxic and antitumor potential has been shown. However, knowledge concerning activities of its derivatives is limited. Herein, a series of usnic acid derivatives were synthesized and their antiproliferative potency against cancer cells of different origin was assessed. Some of the synthesized compounds were more active than usnic acid. Compounds 2a and 2b inhibited survival of all tested cancer cell lines in a dose- and time-dependent manner. Their IC50 values after 48 h of treatment were ca. 3 μM for MCF-7 and PC-3 cells and 1 μM for HeLa cells, while 3a and 3b revealed antiproliferative activity only against HeLa cells. All active usnic acid derivatives induced G0/G1 arrest and a drop in the fraction of HeLa cells in the S and G2/M phases. Compounds 2a and 2b decreased the clonogenic potential of the cancer cells evaluated and induced cell cycle arrest at the G0/G1 phase and apoptosis in MCF-7 cells. Moreover, they induced massive cytoplasmic vacuolization, which was associated with elevated dynein-dependent endocytosis, a process that has not been reported for usnic acid and indicates a novel mechanism of action of its synthetic derivatives. This work also shows that naturally occurring usnic acids are promising lead compounds for the synthesis of derivatives with more favorable properties against cancer cells.
Publication typeIn press (online first, early view)
Author Agnieszka Pyrczak-Felczykowska
Agnieszka Pyrczak-Felczykowska,,
-
, Rajeshwar Narlawar
Rajeshwar Narlawar,,
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, Anna Pawlik (FB / DMBG) - [Akademia Wychowania Fizycznego i Sportu mi. Jędrzeja Śniadeckiego w Gdańsku]
Anna Pawlik,,
- Katedra Biologii i Genetyki Medycznej
- Akademia Wychowania Fizycznego i Sportu mi. Jędrzeja Śniadeckiego w Gdańsku
, Beata Guzow-Krzemińska (FB / DPTNC)
Beata Guzow-Krzemińska,,
- Department of Plant Taxonomy and Nature Conservation
, Damian Artymiuk (FB)
Damian Artymiuk,,
- Faculty of Biology
, Aleksandra Hać (FB / DMBG)
Aleksandra Hać,,
- Katedra Biologii i Genetyki Medycznej
, Kamil Ryś (FB / DMBG)
Kamil Ryś,,
- Katedra Biologii i Genetyki Medycznej
, Louis M. Rendina
Louis M. Rendina,,
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, Tristan A. Reekie
Tristan A. Reekie,,
-
, Anna Herman-Antosiewicz (FB / DMBG)
Anna Herman-Antosiewicz,,
- Katedra Biologii i Genetyki Medycznej
et al.`
Journal seriesJournal of Natural Products, ISSN 0163-3864, (A 35 pkt)
Issue year2019
Noonline first
Pages1-11
Publication size in sheets0.5
ASJC Classification1605 Organic Chemistry; 2707 Complementary and alternative medicine; 3002 Drug Discovery; 3003 Pharmaceutical Science; 3004 Pharmacology; 1313 Molecular Medicine; 1602 Analytical Chemistry
DOIDOI:10.1021/acs.jnatprod.8b00980
URL https://doi.org/10.1021/acs.jnatprod.8b00980
Languageen angielski
Score (nominal)35
ScoreMinisterial score = 35.0, 18-07-2019, ArticleFromJournal
Ministerial score (2013-2016) = 35.0, 18-07-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2017 = 1.487; WoS Impact Factor: 2017 = 3.885 (2) - 2017=3.904 (5)
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