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

Permanent link
https://hdl.handle.net/10037/21500
DOI
https://doi.org/10.3390/molecules26113268
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Date
2021-05-30
Type
Journal article
Tidsskriftartikkel
Peer reviewed

Author
Håheim, Katja Stangeland; Lindback, Emil; Tan, Kah Ni; Albrigtsen, Marte; Helgeland, Ida Therese Urdal; Clemence, Lauga; Matringe, Theodora; Kennedy, Emily K.; Andersen, Jeanette Hammer; Avery, Vicky M.; Sydnes, Magne Olav
Abstract
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).
Publisher
MDPI
Citation
Håheim KS, Lindback E, Tan, Albrigtsen M, Helgeland IT, Clemence, Matringe, Kennedy, Andersen JH, Avery, Sydnes MO. Synthesis and Evaluation of the Tetracyclic Ring-System of Isocryptolepine and Regioiso-Mers for Antimalarial, Antiproliferative and Antimicrobial Activities. Molecules. 2021;26
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