Cytokinin oxidase/dehydrogenase inhibitors: outlook for selectivity and high efficiency

0562506 - ÚEB 2023 RIV GB eng J - Journal Article
Nisler, Jaroslav - Pěkná, Z. - Končitíková, R. - Klimeš, P. - Kadlecová, A. - Murvanidze, N. - Werbrouck, S. - Plačková, Lenka - Kopečný, D. - Zalabák, David - Spíchal, L. - Strnad, Miroslav
Cytokinin oxidase/dehydrogenase inhibitors: outlook for selectivity and high efficiency.
Journal of Experimental Botany. Roč. 73, č. 14 (2022), s. 4806-4817. ISSN 0022-0957. E-ISSN 1460-2431
R&D Projects: GA ČR(CZ) GA21-07661S; GA TA ČR(CZ) TP01010037; GA MŠMT(CZ) EF16_019/0000827
Institutional support: RVO:61389030
Keywords : Agriculture * biotechnology * Caenorhabditis elegans * CKX inhibitor * cytokinin * cytokinin oxidase/dehydrogenase * diphenylurea * nematodes * plant hormones * plant tissue culture
OECD category: Biochemistry and molecular biology
Impact factor: 6.9, year: 2022
Method of publishing: Open access
https://doi.org/10.1093/jxb/erac201

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.
Permanent Link: https://hdl.handle.net/11104/0334826