Cancer represents one of the most important and often fatal threats in the human population. Regarding the natural products, the purine scaffold appears in the purine bases in nucleic acids. Purine and its natural derivatives display a number of pharmacological effects. Previous investigations revealed that different compounds bearing the purine scaffold in their molecules belong to a group of potent agents for cancer treatment. Therefore, this review focuses on summarizing recently designed agents for potential cancer treatment bearing the purine scaffold as the key structural motif in the molecules. The reviewed structures clearly show the advantages and disadvantages of different substituents of the key scaffold that affect the final cytotoxic effects of the studied structures. The structure-activity relationship analysis shows a summary of different but potent compounds mentioned in this review and identifies the compounds receiving priority importance due to their high cytotoxicity and exceptional physicochemical characteristics. The effects of metal coordination, the formation of convenient conjugated molecules, and supramolecular self-assembly resulting in the production of biologically active nanovesicles and other nanoassemblies are also demonstrated. The reviewed original studies clearly showed the possible advantages of (a) metal ion coordination, (b) the formation of conjugates, and (c) designing smart and biocompatible nanoassemblies for biological activity in comparison with the characteristics of the parent compounds. This review is based on the most recent articles published in the last two years, 2023-2024, and it represents work with a highly interdisciplinary nature. Even if these original articles are not too numerous within the given period, the investigations published therein have clearly documented the importance of the purine scaffold in pharmacology and in medicinal and supramolecular chemistry.

• Publication type
• Journal Article MeSH
• Review MeSH

Plant hormone cytokinins are perceived by a subfamily of sensor histidine kinases (HKs), which via a two-component phosphorelay cascade activate transcriptional responses in the nucleus. Subcellular localization of the receptors proposed the endoplasmic reticulum (ER) membrane as a principal cytokinin perception site, while study of cytokinin transport pointed to the plasma membrane (PM)-mediated cytokinin signalling. Here, by detailed monitoring of subcellular localizations of the fluorescently labelled natural cytokinin probe and the receptor ARABIDOPSIS HISTIDINE KINASE 4 (CRE1/AHK4) fused to GFP reporter, we show that pools of the ER-located cytokinin receptors can enter the secretory pathway and reach the PM in cells of the root apical meristem, and the cell plate of dividing meristematic cells. Brefeldin A (BFA) experiments revealed vesicular recycling of the receptor and its accumulation in BFA compartments. We provide a revised view on cytokinin signalling and the possibility of multiple sites of perception at PM and ER.

• MeSH
• Arabidopsis cytology   genetics   metabolism   MeSH
• Brefeldin A pharmacology   MeSH
• Cell Membrane metabolism   MeSH
• Cytokinins chemistry   metabolism   MeSH
• Endoplasmic Reticulum metabolism   MeSH
• Fluorescent Dyes chemistry   metabolism   MeSH
• Plants, Genetically Modified MeSH
• Meristem cytology   metabolism   MeSH
• Protein Kinases genetics   metabolism   MeSH
• Arabidopsis Proteins genetics   metabolism   MeSH
• Receptors, Cell Surface genetics   metabolism   MeSH
• Recombinant Fusion Proteins genetics   metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Green Fluorescent Proteins genetics   metabolism   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Brefeldin A MeSH
• Cytokinins MeSH
• Fluorescent Dyes MeSH
• Protein Kinases MeSH
• Arabidopsis Proteins MeSH
• Receptors, Cell Surface MeSH
• Recombinant Fusion Proteins MeSH
• WOL protein, Arabidopsis MeSH Browser
• Green Fluorescent Proteins MeSH

Five poplar CHASE-containing histidine kinase receptors bind cytokinins and display kinase activities. Both endogenous isoprenoid and aromatic cytokinins bind to the receptors in live cell assays. Cytokinins are phytohormones that play key roles in various developmental processes in plants. The poplar species Populus × canadensis, cv. Robusta, is the first organism found to contain aromatic cytokinins. Here, we report the functional characterization of five CHASE-containing histidine kinases from P. × canadensis: PcHK2, PcHK3a, PcHK3b, PcHK4a and PcHK4b. A qPCR analysis revealed high transcript levels of all PcHKs other than PcHK4b across multiple poplar organs. The ligand specificity was determined using a live cell Escherichia coli assay and we provide evidence based on UHPLC-MS/MS data that ribosides can be true ligands. PcHK2 exhibited higher sensitivity to iP-type cytokinins than the other receptors, while PcHK3a and PcHK3b bound these cytokinins much more weakly, because they possess two isoleucine residues that clash with the cytokinin base and destabilize its binding. All receptors display kinase activity but their activation ratios in the presence/absence of cytokinin differ significantly. PcHK4a displays over 400-fold higher kinase activity in the presence of cytokinin, suggesting involvement in strong responses to changes in cytokinin levels. trans-Zeatin was both the most abundant cytokinin in poplar and that with the highest variation in abundance, which is consistent with its strong binding to all five HKs and activation of cytokinin signaling via A-type response regulators. The aromatic cytokinins' biological significance remains unclear, their levels vary diurnally, seasonally, and annually. PcHK3 and PcHK4 display the strongest binding at pH 7.5 and 5.5, respectively, in line with their putative membrane localization in the endoplasmic reticulum and plasma membrane.

• Keywords
• Aromatic cytokinin, Histidine kinase, Hormone, Isoprenoid cytokinin, Poplar, Topolin,
• MeSH
• Cytokinins metabolism   MeSH
• Histidine Kinase metabolism   MeSH
• Populus metabolism   MeSH
• Tandem Mass Spectrometry MeSH
• Terpenes metabolism   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokinins MeSH
• Histidine Kinase MeSH
• Terpenes MeSH

Plant hormones are master regulators of plant growth and development. Better knowledge of their spatial signaling and homeostasis (transport and metabolism) on the lowest structural levels (cellular and subcellular) is therefore crucial to a better understanding of developmental processes in plants. Recent progress in phytohormone analysis at the cellular and subcellular levels has greatly improved the effectiveness of isolation protocols and the sensitivity of analytical methods. This review is mainly focused on homeostasis of two plant hormone groups, auxins and cytokinins. It will summarize and discuss their tissue- and cell-type specific distributions at the cellular and subcellular levels.

• Keywords
• auxin, cellular level, cytokinin, phytohormone metabolism, phytohormone transport, subcellular level,
• MeSH
• Biological Transport MeSH
• Cytokinins metabolism   MeSH
• Plant Physiological Phenomena * MeSH
• Homeostasis * MeSH
• Intracellular Space metabolism   MeSH
• Indoleacetic Acids metabolism   MeSH
• Metabolic Networks and Pathways MeSH
• Organelles metabolism   MeSH
• Plant Growth Regulators metabolism   MeSH
• Plant Cells metabolism   MeSH
• Plant Development * MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Cytokinins MeSH
• Indoleacetic Acids MeSH
• Plant Growth Regulators MeSH