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Fluorescence in Histochemical Reactions
Published in Victoria Vladimirovna Roshchina, Fluorescence of Living Plant Cells for Phytomedicine Preparations, 2020
Victoria Vladimirovna Roshchina
Alkaloids. Some quaternary benzo[c]phenanthridine alkaloids (sanguinarine and chelerythrine, etc.) may fluoresce within cells, binding to DNA (Slaninova et al. 2008). They show the nucleus architecture similarly to common DNA dyes. When they are excited by argon lasers at 488 nm, a scientist can see fluorescence in the 576–700 nm range. The alkaloids can be used as fluorescent DNA probes for living cells in both fluorescence microscopy and flow cytometry, including multiparameter analysis.
Cytotoxic Phenanthridone Alkaloid Constituents of the Amaryllidaceae
Published in Spyridon E. Kintzios, Maria G. Barberaki, Evangelia A. Flampouri, Plants That Fight Cancer, 2019
Jerald J. Nair, Johannes van Staden
TNFs are a group of proinflammatory cytokines that have been implicated in tumor regression, septic shock, and cachexia (Hanahan and Weinberg 2000). The involvement of TNFs in programmed cell death (apoptosis) is well established (Hanahan and Weinberg 2000). As part of the apoptosis trigger mechanism, cellular death signals are conveyed by TNF-α binding to its receptor TNF-R1 or via the Fas ligand binding the Fas receptor (Hanahan and Weinberg 2000). Since current TNF-inhibitory therapeutics only involve protein entities such as Adalimumab, Etanercept, and Infliximab, interest in small molecule drug targets such as alkaloids, fatty acids, phenolics, retinoids, sterols, and terpenes has been gaining momentum as cost-effective and viable alternatives (Paul et al. 2006). To this extent, narciclasine (11) exhibited potent TNF-α inhibitory activity in murine RAW264 macrophages stimulated with LPS (IC50 0.02 µM) (Yamazaki and Kawano 2011). Furthermore, it was observed that although TNF-α inhibition by narciclasine was caused by non-selective inhibition of protein synthesis, the pyrrolo-phenanthridine lycorine was able to inhibit TNF-α production at lower concentrations than those required to inhibit protein synthesis in macrophages (Paul et al. 2006).
Postjunctional Dopamine Receptor Stimulants
Published in M.D. Francesco Amenta, Peripheral Dopamine Pathophysiology, 2019
Recently a new DA receptor stimulant has been described which has been shown in a variety of biochemical and behavioral tests to exert a very selective effect on DA1 receptors in the central nervous system.73 This compound, CY 208-243 ((-)-(6aR)(12bR)-4,6,6a,7,8,12b-hexahydro-7-methylindolo[4,3-ab]-phenanthridine; Sandoz) can be regarded as a breakthrough in medicinal chemistry in that it is the first potent, selective DA1 receptor agonist without a chemically and metabolically unstable catechol group. Its efficacy in stimulating DA-sensitive adenylate cyclase in vitro is not as high as that of fenoldopam,73 and it is less potent on the cardiovascular system,17 but it represents an important advance in that central and cardiovascular responses to submaximal oral doses are maintained for several hours.17,73
Discovery of potent histone deacetylase inhibitors with modified phenanthridine caps
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Wenli Fan, Lin Zhang, Xuejiang Wang, Haiyong Jia, Lei Zhang
In our previous studies, a series of phenanthridine derivatives were developed with high anticancer activities by targeting DNA topoisomerase13. However, the synthesised molecules are extremely low at both aqueous solubility and liposolubility. Moreover, in the in vivo studies using xenograft nude mice model, molecule 8a exhibited obvious hepatotoxicity. Considering the aromatic properties of phenanthridine structure, strong hydrophobic interactions could be formed between phenanthridine fragment and residues in the opening of HDAC active site. Therefore, in discovery of anticancer agents with improved solubility, activity and safety profiles, pharmacophores of phenanthridine was introduced to the cap region in the structure of HDACIs (Figure 1). By targeting HDACs, the toxicity of the designed molecules was considered to be reduced. To decrease the aromaticity of the designed compounds, the B ring in the phenanthridine structure was opened for the introduction of substituents. Hydroxamic acid group was utilised as zinc binding group, aromatic and fatty linkers were introduced, respectively. The synthesised target compounds were investigated in the enzyme inhibitory assay, in vitro antiproliferative screening, cell cycle and apoptosis test.