Design, Synthesis, and Structural Characterization of Novel Diazaphenothiazines with 1,2,3-Triazole Substituents as Promising Antiproliferative Agents.
Morak-Młodawska BeataKrystian PlutaMałgorzata LatochaMałgorzata JeleńDariusz KuśmierzPublished in: Molecules (Basel, Switzerland) (2019)
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).
Keyphrases
- induced apoptosis
- cell cycle arrest
- gene expression
- endothelial cells
- oxidative stress
- endoplasmic reticulum stress
- real time pcr
- cell death
- induced pluripotent stem cells
- signaling pathway
- poor prognosis
- pluripotent stem cells
- dna methylation
- genome wide
- transcription factor
- breast cancer cells
- high resolution
- single cell
- cell proliferation
- atomic force microscopy
- binding protein
- mass spectrometry
- long non coding rna