diphenylurea Dotaz Zobrazit nápovědu
Increasing crop productivity is our major challenge if we are to meet global needs for food, fodder and fuel. Controlling the content of the plant hormone cytokinin is a method of improving plant productivity. Cytokinin oxidase/dehydrogenase (CKO/CKX) is a major target in this regard because it degrades cytokinins. Here, we describe the synthesis and biological activities of new CKX inhibitors derived mainly from diphenylurea. They were tested on four CKX isoforms from maize and Arabidopsis, where the best compounds showed IC50 values in the 10-8 M concentration range. The binding mode of the most efficient inhibitors was characterized from high-resolution crystal complexed structures. Although these compounds do not possess intrinsic cytokinin activity, we have demonstrated their tremendous potential for use in the plant tissue culture industry as well as in agriculture. We have identified a key substance, compound 19, which not only increases stress resistance and seed yield in Arabidopsis, but also improves the yield of wheat, barley and rapeseed grains under field conditions. Our findings reveal that modulation of cytokinin levels via CKX inhibition can positively affect plant growth, development and yield, and prove that CKX inhibitors can be an attractive target in plant biotechnology and agriculture.
- Klíčová slova
- Agriculture, CKX inhibitor, biotechnology, crystal structure, cytokinin, cytokinin oxidase/dehydrogenase, diphenylurea, plant tissue culture, stress, yield,
- MeSH
- Arabidopsis * MeSH
- biotechnologie MeSH
- cytokininy MeSH
- oxidoreduktasy * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokinin oxidase MeSH Prohlížeč
- cytokininy MeSH
- oxidoreduktasy * MeSH
Inhibitors of cytokinin oxidase/dehydrogenase (CKX) reduce the degradation of cytokinins in plants, and this effect can be exploited in agriculture and in plant tissue culture. In this study, we examine the structure-activity relationship of two series of CKX inhibitors based on diphenylurea. The compounds of Series I were derived from the recently published CKX inhibitors 3TFM-2HM and 3TFM-2HE, and we identified key substituents with increased selectivity for maize ZmCKX1 and ZmCKX4a over AtCKX2 from Arabidopsis. Series II contained compounds that further exceled in CKX inhibitory activity as well as in the ease of their synthesis. The best inhibitors exhibited half-maximal inhibitory concentration (IC50) values in low nanomolar ranges with ZmCKX1 and especially with ZmCKX4a, which is generally more resistant to inhibition. The activity of the key compounds was verified in tobacco and lobelia leaf-disk assays, where N6-isopentenyladenine was protected from degradation and promoted shoot regeneration. All the prepared compounds were further tested for toxicity against Caenorhabditis elegans, and the assays revealed clear differences in toxicity between compounds with and without a hydroxyalkyl group. In a broader perspective, this work increases our understanding of CKX inhibition and provides a more extensive portfolio of compounds suitable for agricultural and biotechnological research.
- Klíčová slova
- Caenorhabditis elegans, Agriculture, CKX inhibitor, biotechnology, cytokinin, cytokinin oxidase/dehydrogenase, diphenylurea, nematodes, plant hormones, plant tissue culture,
- MeSH
- Arabidopsis * metabolismus MeSH
- cytokininy * metabolismus MeSH
- kukuřice setá metabolismus MeSH
- oxidoreduktasy metabolismus MeSH
- rostliny metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokinin oxidase MeSH Prohlížeč
- cytokininy * MeSH
- oxidoreduktasy MeSH
Cytokinin oxidase/dehydrogenase (CKX) inhibitors reduce the degradation of cytokinins in plants and thereby may improve the efficiency of agriculture and plant tissue culture-based practices. Here, we report a synthesis and structure-activity relationship study of novel urea derivatives concerning their CKX inhibitory activity. The best compounds showed sub-nanomolar IC50 values with maize ZmCKX1, the lowest value yet documented. Other CKX isoforms of maize (Zea mays) and Arabidopsis were also inhibited very effectively. The binding mode of four compounds was characterized based on high-resolution crystal complex structures. Using the soil nematode Caenorhabditis elegans, and human skin fibroblasts, key CKX inhibitors with low toxicity were identified. These compounds enhanced the shoot regeneration of Lobelia, Drosera, and Plectranthus, as well as the growth of Arabidopsis and Brassica napus. At the same time, a key compound (namely 82), activated a cytokinin primary response gene ARR5:GUS and cytokinin sensor TCSv2:GUS, without activating the Arabidopsis cytokinin receptors AHK3 and AHK4. This strongly implies that the effect of compound 82 is due to the upregulation of cytokinin signalling. Overall, this work presents highly effective and easily prepared CKX inhibitors with a low risk of environmental toxicity for further investigation of their potential in agriculture and biotechnology.
- Klíčová slova
- Arabidopsis, CKX inhibitor, agriculture, biostimulant, biotechnology, cytokinin, cytokinin oxidase/dehydrogenase, diphenylurea, nutrient use efficiency, oilseed rape,
- Publikační typ
- časopisecké články MeSH
- MeSH
- anestetika lokální analýza MeSH
- chromatografie na tenké vrstvě metody MeSH
- karbanilidy analýza MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- anestetika lokální MeSH
- karbanilidy MeSH
- MeSH
- antiprotozoální látky farmakologie MeSH
- chinoliny farmakologie MeSH
- chlorbenzeny farmakologie MeSH
- ethery farmakologie MeSH
- guanidiny farmakologie MeSH
- HeLa buňky MeSH
- karbanilidy farmakologie MeSH
- kokcidióza farmakoterapie veterinární MeSH
- kultivační média MeSH
- kyseliny karboxylové farmakologie MeSH
- nemoci drůbeže farmakoterapie MeSH
- pyridiny farmakologie MeSH
- pyrimidiny farmakologie MeSH
- Toxoplasma účinky léků růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- chinoliny MeSH
- chlorbenzeny MeSH
- ethery MeSH
- guanidiny MeSH
- karbanilidy MeSH
- kultivační média MeSH
- kyseliny karboxylové MeSH
- pyridiny MeSH
- pyrimidiny MeSH
- MeSH
- Aeromonas izolace a purifikace MeSH
- agar * MeSH
- bakteriologické techniky metody MeSH
- barvicí látky chemie MeSH
- feces mikrobiologie MeSH
- gramnegativní bakteriální infekce diagnóza mikrobiologie MeSH
- karbanilidy chemie MeSH
- kvartérní amoniové sloučeniny chemie MeSH
- lidé MeSH
- průjem diagnóza mikrobiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- agar * MeSH
- barvicí látky MeSH
- brilliant green MeSH Prohlížeč
- cloflucarban MeSH Prohlížeč
- karbanilidy MeSH
- kvartérní amoniové sloučeniny MeSH
- MeSH
- antiprotozoální látky terapeutické užití MeSH
- benzylové sloučeniny terapeutické užití MeSH
- chinoliny terapeutické užití MeSH
- chlorbenzeny terapeutické užití MeSH
- ethery terapeutické užití MeSH
- guanidiny terapeutické užití MeSH
- karbanilidy terapeutické užití MeSH
- kyseliny karboxylové terapeutické užití MeSH
- myši MeSH
- pyridiny terapeutické užití MeSH
- pyrimidiny terapeutické užití MeSH
- toxoplazmóza farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antiprotozoální látky MeSH
- benzylové sloučeniny MeSH
- chinoliny MeSH
- chlorbenzeny MeSH
- ethery MeSH
- guanidiny MeSH
- karbanilidy MeSH
- kyseliny karboxylové MeSH
- pyridiny MeSH
- pyrimidiny MeSH
- MeSH
- anestetika lokální analýza MeSH
- chemické jevy MeSH
- chemie fyzikální MeSH
- karbanilidy analýza MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anestetika lokální MeSH
- karbanilidy MeSH
