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Key Role of Reactive Oxygen Species (ROS) in Indirubin Derivative-Induced Cell Death in Cutaneous T-Cell Lymphoma Cells
Cutaneous T-cell lymphoma (CTCL) may develop a highly malignant phenotype in its late phase, and patients may profit from innovative therapies. The plant extract indirubin and its chemical derivatives represent new and promising antitumor strategies. This first report on the effects of an indirubin derivative in CTCL cells shows a strong decrease of cell proliferation and cell viability as well as an induction of apoptosis, suggesting indirubin derivatives for therapy of CTCL. As concerning the mode of activity, the indirubin derivative DKP-071 activated the extrinsic apoptosis cascade via caspase-8 and caspase-3 through downregulation of the caspase antagonistic proteins c-FLIP and XIAP. Importantly, a strong increase of reactive oxygen species (ROS) was observed as an immediate early effect in response to DKP-071 treatment. The use of antioxidative pre-treatment proved the decisive role of ROS, which turned out upstream of all other proapoptotic effects monitored. Thus, reactive oxygen species appear as a highly active proapoptotic pathway in CTCL, which may be promising for therapeutic intervention. This pathway can be efficiently activated by an indirubin derivative. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties
Acridine derivatives have attracted considerable interest in numerous areas owing to their attractive physical and chemical properties. Herein, starting from readily available anthranilic acid, an efficient synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine derivatives was accomplished via a one-pot double Sonogashira cross-coupling method. The UV-visible absorption and emission properties of the synthesized molecules have been examined. Additionally, theoretical studies based on density functional theory (DFT/B3LYP/6-31G(d)) were carried out.
Crucial Role of Reactive Oxygen Species (ROS) for the Proapoptotic Effects of Indirubin Derivatives in Cutaneous SCC Cells
Efficient drugs are needed for countering the worldwide high incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis. Indirubin derivatives represent promising candidates, but their effects in cSCC cells have not been reported before. Here, we investigated the efficacy of three indirubin derivatives (DKP-071,-073 and-184) in four cSCC cell lines. High efficacy was seen in SCL-I, SCL-II, SCC-12 and SCC-13, resulting in up to 80% loss of cell proliferation, 60% loss of cell viability and 30% induced apoptosis (10 µM). Apoptosis was further enhanced in com-binations with TNF-related apoptosis-inducing ligand (TRAIL). Induction of reactive oxygen species (ROS) appeared as critical for these effects. Thus, antioxidative pretreatment completely abol-ished apoptosis as well as restored cell proliferation and viability. Concerning the pathways, com-plete activation of caspases cascades (caspases-3,-4,-6,-7,-8 and-9), loss of mitochondrial membrane potential, activation of proapoptotic PKCδ (protein kinase C delta), inhibition of STAT3 (sig-nal transducer and activator of transcription 3), downregulation of antiapoptotic XIAP (X-linked inhibitor of apoptosis protein) and survivin as well as upregulation of the proapoptotic Bcl-2 protein Puma and the cell cycle inhibitor p21 were obtained. Importantly, all activation steps were pre-vented by antioxidants, thus proving ROS as a master regulator of indirubins’ antitumor effects. ROS induction presently develops as an important issue in anticancer therapy. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles
A two-step palladium-catalyzed procedure based on Suzuki–Miyaura cross coupling, followed by a double Buchwald–Hartwig reaction, allows for the synthesis of pharmaceutically relevant benzo[4,5]furo[3,2-b]indoles in moderate to very good yield. The synthesized compounds have been analyzed with regard to their inhibitory activity (IC50) of nucleotide pyrophosphatases h-NPP1 and h-NPP3. The activity lies in the nanomolar range. The results were rationalized based on docking studies. © 2019 Do et al.
One Pot Synthesis and Characterization of Mono and Di-Substituted Azo-Containing Amides
Azo-containing amides and their derivatives were synthesized by the reaction of 4-(phenyldiazenyl)aniline with different substituted benzoyl chlorides. The characterization of these synthesized compounds were based on their IR, 1H NMR spectra and elemental analysis with excellent yields.
Isolation of phytochemical constituents from hunteria umbellata k. Schum
Hunteria umbellata K. Schum has been reported for the treatment of diabetes in Nigeria. In the present study, the ethanolic extract of dried leaves of Hunteria umbellata K. Schum was investigated for the chemical principles. The isolated pure compounds were characterized by NMR, IR and Mass spectral studies. Ursolic acid (1), oleanolic acid (2) and squalene (3) were the main constituents isolated from the extract.