Journal Article

DKFZ-2023-02435

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Quinoline-based thiazolyl-hydrazones target cancer cells through autophagy inhibition.

Ćurčić, V. ; Olszewski, M. ; Maciejewska, N. ; Višnjevac, A. ; Srdić-Rajić, T. ; Dobričić, V. ; García-Sosa, A. T. ; Kokanov, S. B. ; Araškov, J. B. ; Silvestri, R. ; Schüle, R.DKFZ* ; Jung, M.DKFZ* ; Nikolić, M. ; Filipović, N. R.

2024
Wiley-VCH Weinheim

Abstract: Heterocyclic pharmacophores such as thiazole and quinoline rings have a significant role in medicinal chemistry. They are considered privileged structures since they constitute several Food and Drug Administration (FDA)-approved drugs for cancer treatment. Herein, we report the synthesis, in silico evaluation of the ADMET profiles, and in vitro investigation of the anticancer activity of a series of novel thiazolyl-hydrazones based on the 8-quinoline (1a-c), 2-quinoline (2a-c), and 8-hydroxy-2-quinolyl moiety (3a-c). The panel of several human cancer cell lines and the nontumorigenic human embryonic kidney cell line HEK-293 were used to evaluate the compound-mediated in vitro anticancer activities, leading to [2-(2-(quinolyl-8-ol-2-ylmethylene)hydrazinyl)]-4-(4-methoxyphenyl)-1,3-thiazole (3c) as the most promising compound. The study revealed that 3c blocks the cell-cycle progression of a human colon cancer cell line (HCT-116) in the S phase and induces DNA double-strand breaks. Also, our findings demonstrate that 3c accumulates in lysosomes, ultimately leading to the cell death of the hepatocellular carcinoma cell line (Hep-G2) and HCT-116 cells, by the mechanism of autophagy inhibition.

Keyword(s): DNA damage ; anticancer activity ; hydrazonyl-thiazoles ; lysosomes targeting ; quinoline derivatives

Note: 2024 Feb;357(2):e2300426

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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