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@article{2210998,
author = {Gargantilla, Marta and Persoons, Leentje and Kauerová, Tereza and del Rio, Natalia and Daelemans, Dirk and Priego, EvaandMaria and Kollár, Peter and PerezandPerez, MariaandJesus},
article_location = {BASEL},
article_number = {7},
doi = {http://dx.doi.org/10.3390/ph15070835},
keywords = {tubulin polymerization inhibitors; colchicine site; salicylanilides; niclosamide; signal transducer and activator of transcription (STAT3) inhibitors},
language = {eng},
issn = {1424-8247},
journal = {Pharmaceuticals},
title = {Hybridization Approach to Identify Salicylanilides as Inhibitors of Tubulin Polymerization and Signal Transducers and Activators of Transcription 3 (STAT3)},
url = {https://www.mdpi.com/1424-8247/15/7/835/htm},
volume = {15},
year = {2022}
}
TY - JOUR
ID - 2210998
AU - Gargantilla, Marta - Persoons, Leentje - Kauerová, Tereza - del Rio, Natalia - Daelemans, Dirk - Priego, Eva-Maria - Kollár, Peter - Perez-Perez, Maria-Jesus
PY - 2022
TI - Hybridization Approach to Identify Salicylanilides as Inhibitors of Tubulin Polymerization and Signal Transducers and Activators of Transcription 3 (STAT3)
JF - Pharmaceuticals
VL - 15
IS - 7
SP - 1-18
EP - 1-18
PB - MDPI
SN - 14248247
KW - tubulin polymerization inhibitors
KW - colchicine site
KW - salicylanilides
KW - niclosamide
KW - signal transducer and activator of transcription (STAT3) inhibitors
UR - https://www.mdpi.com/1424-8247/15/7/835/htm
N2 - The superimposition of the X-ray complexes of cyclohexanediones (i.e., TUB015), described by our research group, and nocodazole, within the colchicine binding site of tubulin provided an almost perfect overlap of both ligands. This structural information led us to propose hybrids of TUB015 and nocodazole using a salicylanilide core structure. Interestingly, salicylanilides, such as niclosamide, are well-established signal transducers and activators of transcription (STAT3) inhibitors with anticancer properties. Thus, different compounds with this new scaffold have been synthesized with the aim to identify compounds inhibiting tubulin polymerization and/or STAT3 signaling. As a result, we have identified new salicylanilides (6 and 16) that showed significant antiproliferative activity against a panel of cancer cells. Both compounds were able to reduce the levels of p-STAT3(Tyr705) without affecting the total expression of STAT3. While compound 6 inhibited tubulin polymerization and arrested the cell cycle of DU145 cells at G2/M, similar to TUB015, compound 16 showed a more potent effect on inhibiting STAT3 phosphorylation and arrested the cell cycle at G1/G0, similar to niclosamide. In both cases, no toxicity towards PBMC cells was detected. Thus, the salicylanilides described here represent a new class of antiproliferative agents affecting tubulin polymerization and/or STAT3 phosphorylation.
ER -
GARGANTILLA, Marta, Leentje PERSOONS, Tereza KAUEROVÁ, Natalia DEL RIO, Dirk DAELEMANS, Eva-Maria PRIEGO, Peter KOLLÁR and Maria-Jesus PEREZ-PEREZ. Hybridization Approach to Identify Salicylanilides as Inhibitors of Tubulin Polymerization and Signal Transducers and Activators of Transcription 3 (STAT3). \textit{Pharmaceuticals}. BASEL: MDPI, 2022, vol.~15, No~7, p.~1-18. ISSN~1424-8247. Available from: https://dx.doi.org/10.3390/ph15070835.
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