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Open AccessArticle

Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents

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Department of Organic Chemistry, Faculty of Pharmaceutical Sciences, The Medical University of Silesia, Jagiellońska 4, 41-200 Sosnowiec, Poland
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Department of Cell Biology, Faculty of Pharmaceutical Sciences, The Medical University of Silesia, Jedności 8, 41-200 Sosnowiec, Poland
*
Author to whom correspondence should be addressed.
Molecules 2019, 24(23), 4388; https://doi.org/10.3390/molecules24234388
Received: 28 October 2019 / Revised: 19 November 2019 / Accepted: 27 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue Facing Novel Challenges in Drug Discovery)
A series of novel 1,2,3-triazole-diazphenothiazine hybrids was designed, synthesized, and evaluated for anticancer activity against four selected human tumor cell lines (SNB-19, Caco-2, A549, and MDA-MB231). The majority of the synthesized compounds exhibited significant potent activity against the investigated cell lines. Among them, compounds 1d and 4c showed excellent broad spectrum anticancer activity, with IC50 values ranging from 0.25 to 4.66 μM and 0.25 to 6.25 μM, respectively. The most promising compound 1d, possessing low cytotoxicity against normal human fibroblasts NHFF, was used for gene expression analysis using reverse transcription–quantitative real-time PCR (RT–qPCR). The expression of H3, TP53, CDKN1A, BCL-2, and BAX genes revealed that these compounds inhibited the proliferation in all cells (H3) and activated mitochondrial events of apoptosis (BAX/BCL-2). View Full-Text
Keywords: diazaphenothiazines; 1,2,3-triazole ring; antiproliferative activity; intracellular apoptosis pathway; H3; TP53; CDKN1A; BAX/BCL-2 ratio diazaphenothiazines; 1,2,3-triazole ring; antiproliferative activity; intracellular apoptosis pathway; H3; TP53; CDKN1A; BAX/BCL-2 ratio
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Morak-Młodawska, B.; Pluta, K.; Latocha, M.; Jeleń, M.; Kuśmierz, D. Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents. Molecules 2019, 24, 4388.

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