Unravelling the anticancer potency of 1,2,4-triazole-N-arylamide hybrids through inhibition of STAT3: synthesis and in silico mechanistic studies.
1,2,4-Triazoles
Anticancer
Docking
Pharmacokinetic
STAT3
Journal
Molecular diversity
ISSN: 1573-501X
Titre abrégé: Mol Divers
Pays: Netherlands
ID NLM: 9516534
Informations de publication
Date de publication:
Feb 2021
Feb 2021
Historique:
received:
06
07
2020
accepted:
06
08
2020
pubmed:
25
8
2020
medline:
3
9
2021
entrez:
25
8
2020
Statut:
ppublish
Résumé
The discovery of potent STAT3 inhibitors has gained noteworthy impetus in the last decade. In line with this trend, considering the proven biological importance of 1,2,4-triazoles, herein, we are reporting the design, synthesis, pharmacokinetic profiles, and in vitro anticancer activity of novel C3-linked 1,2,4-triazole-N-arylamide hybrids and their in silico proposed mechanism of action via inhibition of STAT3. The 1,2,4-triazole scaffold was selected as a privilege ring system that is embedded in core structures of a variety of anticancer drugs which are either in clinical use or still under clinical trials. The designed 1,2,4-triazole derivatives were synthesized by linking the triazole-thione moiety through amide hydrophilic linkers with diverse lipophilic fragments. In silico study to predict cytotoxicity of the new hybrids against different kinds of human cancer cell lines as well as the non-tumor cells was conducted. The multidrug-resistant human breast adenocarcinoma cells (MDA-MB-231) was found most susceptible to the cytotoxic effect of synthesized compounds and hence were selected to evaluate the in vitro anticancer activity. Four of the designed derivatives showed promising cytotoxicity effects against selected cancer cells, among which compound 12 showed the highest potency (IC
Identifiants
pubmed: 32830299
doi: 10.1007/s11030-020-10131-0
pii: 10.1007/s11030-020-10131-0
doi:
Substances chimiques
Antineoplastic Agents
0
Ligands
0
STAT3 Transcription Factor
0
Triazoles
0
1,2,4-triazole
288-88-0
Doxorubicin
80168379AG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
403-420Références
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