Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial, Antiproliferative and Antimicrobial Activities

Katja S. Håheim; Emil Lindbäck; Kah Ni Tan; Marte Albrigtsen; Ida T. Urdal Helgeland; Clémence Lauga; Théodora Matringe; Emily K. Kennedy; Jeanette H. Andersen; Vicky M. Avery; Magne O. Sydnes

doi:10.3390/molecules26113268

Molecules (May 2021)

Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioisomers for Antimalarial, Antiproliferative and Antimicrobial Activities

Katja S. Håheim,
Emil Lindbäck,
Kah Ni Tan,
Marte Albrigtsen,
Ida T. Urdal Helgeland,
Clémence Lauga,
Théodora Matringe,
Emily K. Kennedy,
Jeanette H. Andersen,
Vicky M. Avery,
Magne O. Sydnes

Affiliations

Katja S. Håheim: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway
Emil Lindbäck: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway
Kah Ni Tan: Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, QLD 4111, Australia
Marte Albrigtsen: The Norwegian College of Fishery Science, Marbio, UiT—The Arctic University of Norway, Breivika, NO-9037 Tromsø, Norway
Ida T. Urdal Helgeland: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway
Clémence Lauga: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway
Théodora Matringe: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway
Emily K. Kennedy: Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, QLD 4111, Australia
Jeanette H. Andersen: The Norwegian College of Fishery Science, Marbio, UiT—The Arctic University of Norway, Breivika, NO-9037 Tromsø, Norway
Vicky M. Avery: Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, QLD 4111, Australia
Magne O. Sydnes: Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, NO-4036 Stavanger, Norway

DOI: https://doi.org/10.3390/molecules26113268
Journal volume & issue: Vol. 26, no. 11
p. 3268

Abstract

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A series of novel quinoline-based tetracyclic ring-systems were synthesized and evaluated in vitro for their antiplasmodial, antiproliferative and antimicrobial activities. The novel hydroiodide salts 10 and 21 showed the most promising antiplasmodial inhibition, with compound 10 displaying higher selectivity than the employed standards. The antiproliferative assay revealed novel pyridophenanthridine 4b to be significantly more active against human prostate cancer (IC50 = 24 nM) than Puromycin (IC50 = 270 nM) and Doxorubicin (IC50 = 830 nM), which are used for clinical treatment. Pyridocarbazoles 9 was also moderately effective against all the employed cancer cell lines and moreover showed excellent biofilm inhibition (9a: MBIC = 100 µM; 9b: MBIC = 100 µM).

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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