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Novel thidiazuron-derived inhibitors of cytokinin oxidase/dehydrogenase

SYSNO ASEP	0463803
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Novel thidiazuron-derived inhibitors of cytokinin oxidase/dehydrogenase
Author(s)	Nisler, Jaroslav (UEB-Q)_{RID, ORCID} Kopečný, D. (CZ) Končitíková, R. (CZ) Zatloukal, Marek (UEB-Q)_ORCID Bazgier, Václav (UEB-Q)_{ORCID, RID} Berka, K. (CZ) Zalabák, D. (CZ) Briozzo, P. (FR) Strnad, Miroslav (UEB-Q)_{RID, ORCID} Spíchal, Lukáš (UEB-Q)_{RID, ORCID}
Source Title	Plant Molecular Biology. - : Springer - ISSN 0167-4412 Roč. 92, 1-2 (2016), s. 235-248
Number of pages	14 s.
Language	eng - English
Country	NL - Netherlands
Keywords	Cytokinin oxidase/dehydrogenase ; Crystal structure ; Molecular docking
Subject RIV	EB - Genetics ; Molecular Biology
R&D Projects	LO1204 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	GA15-22322S GA ČR - Czech Science Foundation (CSF)
Institutional support	UEB-Q - RVO:61389030
UT WOS	000382336500016
DOI	10.1007/s11103-016-0509-0
Annotation	Two 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. TDZ thus increases the lifetime of cytokinins and their effects in plants. We used in silico modeling to design, synthesize and characterize twenty new TDZ derivatives with improved inhibitory properties. Two compounds, namely 1-[1,2,3]thiadiazol-5-yl-3-(3-trifluoromethoxy-phenyl)urea (3FMTDZ) and 1-[2-(2-hydroxyethyl)phenyl]-3-(1,2,3-thiadiazol-5-yl)urea (HETDZ), displayed up to 15-fold lower IC (50) values compared with TDZ for AtCKX2 from Arabidopsis thaliana and ZmCKX1 and ZmCKX4a from Zea mays. Binding modes of 3FMTDZ and HETDZ were analyzed by X-ray crystallography. Crystal structure complexes, solved at 2.0 resolution, revealed that HETDZ and 3FMTDZ bound differently in the active site of ZmCKX4a: the thiadiazolyl ring of 3FMTDZ was positioned over the isoalloxazine ring of FAD, whereas that of HETDZ had the opposite orientation, pointing toward the entrance of the active site. The compounds were further tested for cytokinin activity in several cytokinin bioassays. We suggest that the combination of simple synthesis, lowered cytokinin activity, and enhanced inhibitory effects on CKX isoforms, makes 3FMTDZ and HETDZ suitable candidates for in vivo studies.
Workplace	Institute of Experimental Botany
Contact	David Klier, knihovna@ueb.cas.cz, Tel.: 220 390 469
Year of Publishing	2017

Number of the records: 1