Design, synthesis, in vitro potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties.

Autor: Gamal El-Din MM; Pharmaceutical and Drug Industries Research Division, National Research Centre , Dokki-Giza , Egypt., El-Gamal MI; Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah , Sharjah , UAE.; Sharjah Institute for Medical Research, University of Sharjah , Sharjah , UAE.; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura , Mansoura , Egypt., Abdel-Maksoud MS; Pharmaceutical and Drug Industries Research Division, National Research Centre , Dokki-Giza , Egypt., Yoo KH; Chemical Kinomics Research Center, Korea Institute of Science and Technology , Seoul , Republic of Korea., Oh CH; Center for Biomaterials, Korea Institute of Science and Technology , Seoul , Republic of Korea.; Department of Biomolecular Science, University of Science and Technology , Daejeon , Republic of Korea.
Jazyk: angličtina
Zdroj: Journal of enzyme inhibition and medicinal chemistry [J Enzyme Inhib Med Chem] 2019 Dec; Vol. 34 (1), pp. 1534-1543.
DOI: 10.1080/14756366.2019.1653292
Abstrakt: A new series of triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h - j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μM, and thus were next examined in 5-dose testing mode to detect their IC 50 value. The four compounds showed stronger antiproliferative activities upon comparing their results with sorafenib as a reference compound. Among them, compounds 1j and 1l possessing N- ethylpiperazinyl and N- benzylpiperazinyl terminal moiety through ethylene linker showed the greatest values of mean percentage inhibition (97.72 and 107.18%, respectively) over the 58-cell line panel at 10 μM concentration. The IC 50 values of compound 1j over several cancer cell lines were in submicromolar scale (0.26 ∼ 0.38 μM). Moreover, the compounds 1j and 1l showed highly inhibitory activities (99.17 and 97.92%) against V600E-B-RAF kinase.
Databáze: MEDLINE
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