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
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).
