A library of 3-aryl-3-azetidinyl acetic acid methyl ester derivatives was prepared from N-Boc-3-azetidinone employing the Horner-Wadsworth-Emmons reaction, rhodium(I)-catalyzed conjugate addition of arylboronic acids, and subsequent elaborations to obtain N-unprotected hydrochlorides, N-alkylated and N-acylated azetidine derivatives. The compounds were evaluated for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, revealing several derivatives to possess AChE inhibition comparable to that of the AChE inhibitor rivastigmine. The binding mode of the AChE inhibitor donepezil and selected active compounds 26 and 27 within the active site of AChE was studied using molecular docking.
View Article and Find Full Text PDFAuxins and cytokinins are two major families of phytohormones that control most aspects of plant growth, development and plasticity. Their distribution in plants has been described, but the importance of cell- and subcellular-type specific phytohormone homeostasis remains undefined. Herein, we revealed auxin and cytokinin distribution maps showing their different organelle-specific allocations within the Arabidopsis plant cell.
View Article and Find Full Text PDFIsoprenoid cytokinins are a class of naturally occurring plant signaling molecules. A series of prepared compounds derived from isoprenoid cytokinins (isopentenyladenine, trans-zeatin and cis-zeatin) with attached 2'-deoxy-d-ribose or 2',3'-dideoxy-d-ribose at the N position of the purine were prepared and their biological activities were examined. Different synthetic approaches were employed.
View Article and Find Full Text PDFSolubility of growth regulators is essential for their use in agriculture. Four new cytokinin salts─6-benzylaminopurine mesylate (), 6-(2-hydroxybenzylamino)purine mesylate (), 6-(3-hydroxybenzylamino)purine mesylate (), and 6-(3-methoxybenzylamino)purine mesylate ()─were synthesized, and their crystal structures were determined to clarify structural influence on water solubility. The mesylates were several orders of magnitude more water-soluble than the parent CKs.
View Article and Find Full Text PDFSulfated phenolic acids are widely occurring metabolites in plants, including fruits, vegetables and crops. The untargeted UHPLC-QTOF-MS metabolomics of more than 50 samples from plant, fungi and algae lead to the discovery of a small group of sulfated metabolites derived from phenolic acids. These compounds were detected in land plants for the first time.
View Article and Find Full Text PDFMembers of the Viola genus play important roles in traditional Asian herbal medicine. This study investigates the ability of Viola odorata L. extracts to inhibit Na,K-ATPase, an essential animal enzyme responsible for membrane potential maintenance.
View Article and Find Full Text PDFKinetin (N-furfuryladenine), a plant growth substance of the cytokinin family, has been shown to modulate aging and various age-related conditions in animal models. Here we report the synthesis of kinetin isosteres with the purine ring replaced by other bicyclic heterocycles, and the biological evaluation of their activity in several in vitro models related to neurodegenerative diseases. Our findings indicate that kinetin isosteres protect Friedreich́s ataxia patient-derived fibroblasts against glutathione depletion, protect neuron-like SH-SY5Y cells from glutamate-induced oxidative damage, and correct aberrant splicing of the ELP1 gene in fibroblasts derived from a familial dysautonomia patient.
View Article and Find Full Text PDFIn order to pinpoint phytohormone changes associated with enhanced heat stress tolerance, the complex phytohormone profiles [cytokinins, auxin, abscisic acid (ABA), jasmonic acid (JA), salicylic acid and ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC)] were compared in after direct heat shock (45°C, 3 h) and in heat-stressed pre-acclimated plants (1 h at 37°C followed by 2 h at optimal temperature 20°C). Organ-specific responses were followed in shoot apices, leaves, and roots immediately after heat shock and after 24-h recovery at 20°C. The stress strength was evaluated membrane ion leakage and the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) and antioxidant enzymes [superoxide dismutases, guaiacol peroxidases (POD), catalases, ascorbate peroxidases (APX)].
View Article and Find Full Text PDFCytokinins are naturally occurring substances that act as plant growth regulators promoting plant growth and development, including shoot initiation and branching, and also affecting apical dominance and leaf senescence. Aromatic cytokinin 6-benzylaminopurine (BAP) has been widely used in micropropagation systems and biotechnology. However, its 9-glucoside (BAP9G) accumulates in explants, causing root inhibition and growth heterogenity.
View Article and Find Full Text PDFRho-associated serine/threonine kinases (ROCKs) are principal regulators of the actin cytoskeleton that regulate the contractility, shape, motility, and invasion of cells. We explored the relationships between structure and anti-ROCK2 activity in a group of purine derivatives substituted at the C6 atom by piperidin-1-yl or azepan-1-yl groups. Structure-activity relationship (SAR) analyses suggested that anti-ROCK activity is retained, and may be further increased, by substitution of the parent compounds at the C2 atom or by expansion of the C6 side chain.
View Article and Find Full Text PDFVirulent strains of cause a range of disease symptoms, many of which can be mimicked by application of cytokinin. Both virulent and avirulent strains produce a complex of cytokinins, most of which can be derived from tRNA degradation. To test the three current hypotheses regarding the involvement of cytokinins as virulence determinants, we used PCR to detect specific genes, previously associated with a linear virulence plasmid, including two methyl transferase genes ( and ) and (dimethyl transferase), of multiple strains of .
View Article and Find Full Text PDFSynthesis of [ N ] purine labeled cytokinine glycosides derived from zeatins and topolins containing a 9-β-d, 7-β-d-glucopyranosyl, or 9-β-d-ribofuranosyl group is described. These N -substituted adenine derivatives are intended as internal analytic standards for phytohormone analysis. All labeled compounds were prepared from 6-chloro[ N ]purine (1).
View Article and Find Full Text PDFCytokinins (CKs) and their metabolites and derivatives are essential for cell division, plant growth regulation and development. They are typically found at minute concentrations in plant tissues containing very complicated biological matrices. Therefore, defined standards labelled with stable isotopes are required for precise metabolic profiling and quantification of CKs, as well as elucidation of CK biosynthesis in various plant species.
View Article and Find Full Text PDFStress-induced senescence is a global agro-economic problem. Cytokinins are considered to be key plant anti-senescence hormones, but despite this practical function their use in agriculture is limited because cytokinins also inhibit root growth and development. We explored new cytokinin analogs by synthesizing a series of 1,2,3-thiadiazol-5-yl urea derivatives.
View Article and Find Full Text PDFCytokinin ribosides (N-substituted adenosines) have demonstrated anticancer activity in various cultured cell lines, several xenografts and even a small clinical trial. Effects of kinetin riboside, N-benzyladenosine (BAR) and N-isopentenyladenosine on various parameters related to apoptosis have also been reported, but not directly compared with those of the highly active naturally occurring aromatic cytokinins oTR (ortho-topolin riboside) and 2OH3MeOBAR (N-(2-hydroxy-3-methoxybenzyl)adenosine). Here we show that 2OH3MeOBAR is the most active cytokinin riboside studied to date (median, 1st quartile, 3rd quartile and range of GI50 in tests with the NCI60 cell panel: 0.
View Article and Find Full Text PDFCytokinins (CKs) are pivotal plant hormones that have crucial roles in plant growth and development. However, their isolation and quantification are usually challenging because of their extremely low levels in plant tissues (pmol g fresh weight). We have developed a simple microscale magnetic immunoaffinity-based method for selective one-step isolation of CKs from very small amounts of plant tissue (less than 0.
View Article and Find Full Text PDFTwo new TDZ derivatives (HETDZ and 3FMTDZ) are very potent inhibitors of CKX and are promising candidates for in vivo studies. Cytokinin hormones regulate a wide range of essential processes in plants. Thidiazuron (N-phenyl-N'-1,2,3-thiadiazol-5-yl urea, TDZ), formerly registered as a cotton defoliant, is a well known inhibitor of cytokinin oxidase/dehydrogenase (CKX), an enzyme catalyzing the degradation of cytokinins.
View Article and Find Full Text PDFCytokinins (CKs) are an important group of phytohormones. Their tightly regulated and balanced levels are essential for proper cell division and plant organ development. Here we report precise quantification of CK metabolites and other phytohormones in maize reproductive organs in the course of pollination and kernel maturation.
View Article and Find Full Text PDFCytokinins represent an important group of plant growth regulators that can modulate several biotechnological processes owing to their ability to influence almost all stages of plant development and growth. In addition, the use of purine based cytokinins with aromatic substituent in C6 position of the purine moiety in tissue culture techniques is currently experiencing a surge in interest, made possible by the ongoing systematic synthesis and study of these compounds. This review article outlines progress in the synthesis of aromatic cytokinins, the in vitro and in vivo effects of these substances and insights gleaned from their synthesis.
View Article and Find Full Text PDFThere is a continuous search for new chemical entities to expand the collection of suitable compounds to increase the efficiency of micropropagation protocols. Two cytokinin (CK) analogues, 2-chloro-6-(3-methoxyphenyl)aminopurine (INCYDE) and CK antagonist 6-(2-hydroxy-3-methylbenzylamino)purine (PI-55) were used as a tool to elucidate the auxin-CK crosstalk under in vitro conditions in the medicinally important plant, Eucomis autumnalis subspecies autumnalis. These compounds were tested at 0.
View Article and Find Full Text PDFHere we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model.
View Article and Find Full Text PDFThe effect of 2-chloro-6-(3-methoxyphenyl)aminopurine [inhibitor of cytokinin degradation (INCYDE)] at 10 nM on growth, biochemical and photosynthetic efficiency in sodium chloride (NaCl)-stressed (75, 100 and 150 mM) tomato plants was investigated. NaCl-induced decline in plant vigor index was slightly reversed by both drenching and foliar application of INCYDE. Foliar application of INCYDE significantly increased the flower number in the control and 75 mM NaCl-supplemented plants, while drenching was more effective in 150 mM NaCl-stressed plants.
View Article and Find Full Text PDFTreatment options for hepatocellular carcinoma using chemotherapeutics at intermediate and advanced stages of disease are limited as patients most rapidly escape from therapy and succumb to disease progression. Mechanisms of the hepatic xenobiotic metabolism are mostly involved in providing chemoresistance to therapeutic compounds. Given the fact that the aberrant activation of cyclin-dependent kinases (CDK) is frequently observed in hepatocellular carcinomas, we focused on the efficacy of the novel compounds BA-12 and BP-14 that antagonize CDK1/2/5/7 and CDK9.
View Article and Find Full Text PDFThe inhibition of overactive CDKs during cancer remains an important strategy in cancer drug development. We synthesized and screened a novel series of 2-substituted-6-biarylmethylamino-9-cyclopentylpurine derivatives for improved CDK inhibitory activity and antiproliferative effects. One of the most potent compounds, 6b, exhibited strong cytotoxicity in the human melanoma cell line G361 that correlated with robust CDK1 and CDK2 inhibition and caspase activation.
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