Synthesis and evaluation of an agrocin 84 toxic moiety (TM84) analogue as a malarial threonyl tRNA synthetase inhibitor?
Organic & Biomolecular Chemistry Pub Date: 2023-06-14 DOI: 10.1039/D3OB00670K
Abstract
An analogue of a toxic moiety (TM84) of natural product agrocin 84 containing threonine amide instead of 2,3-dihydroxy-4-methylpentanamide was prepared and evaluated as a putative Plasmodium falciparum threonyl t-RNA synthetase (PfThrRS) inhibitor. This TM84 analogue features submicromolar inhibitory potency (IC50 = 440 nM) comparable to that of borrelidin (IC50 = 43 nM) and therefore complements chemotypes known to inhibit malarial PfThrRS, which are currently limited to borrelidin and its analogues. The crystal structure of the inhibitor in complex with the E. coli homologue enzyme (EcThrRS) was obtained, revealing crucial ligand–protein interactions that will pave the way for the design of novel ThrRS inhibitors.
Recommended Literature
- [1] Fe/Fe3C@C nanoparticles encapsulated in N-doped graphene–CNTs framework as an efficient bifunctional oxygen electrocatalyst for robust rechargeable Zn–air batteries? Zhiyan Chen,Nan Wu,Yaobing Wang,Bing Wang,Yingde WangJ. Mater. Chem. A, 2018,6, 516-526 10.1039/C7TA08423D
- [2] Emerging enantiomeric resolution materials with homochiral nano-fabrications Ji-Ping WeiNanoscale, 2015,7, 11815-11832 10.1039/C5NR03048J
- [3] Fatty acid positional distribution in colostrum and mature milk of women living in Inner Mongolia, North Jiangsu and Guangxi of China? Long Deng,Qian Zou,Biao Liu,Wenhui Ye,Chengfei Zhuo,Li Chen,Ze-Yuan Deng,Ya-Wei Fan,Jing LiFood Funct., 2018,9, 4234-4245 10.1039/C8FO00787J
- [4] Embedding cyclic nitrone in mesoporous silica particles for EPR spin trapping of superoxide and other radicals? Eric Besson,Stéphane Gastaldi,Emily Bloch,Selma Aslan,Hakim Karoui,Olivier Ouari,Micael HardyAnalyst, 2019,144, 4194-4203 10.1039/C9AN00468H
- [5] Fast-Track to Research Data Management in Experimental Material Science-Setting the Ground for Research Group Level Materials Digitalization. LarsBanko,AlfredLudwig 10.1021/acscombsci.0c00057
- [6] Evolved polymerases facilitate selection of fully 2′-OMe-modified aptamers? Zhixia Liu,Tingjian Chen,Floyd E. RomesbergChem. Sci., 2017,8, 8179-8182 10.1039/C7SC03747C
- [7] Emulsion technologies for multicellular tumour spheroid radiation assays? Kay S. McMillan,Anthony G. McCluskey,Annette Sorensen,Marie Boyd,Michele ZagnoniAnalyst, 2016,141, 100-110 10.1039/C5AN01382H
- [8] Excellent peroxidase mimicking property of CuO/Pt nanocomposites and their application as an ascorbic acid sensor? Xinhuan Wang,Shuangfei Cai,Cui QiAnalyst, 2017,142, 2500-2506 10.1039/C7AN00589J
- [9] Exceptionally high temperature spin crossover in amide-functionalised 2,6-bis(pyrazol-1-yl)pyridine iron(ii) complex revealed by variable temperature Raman spectroscopy and single crystal X-ray diffraction? Max Attwood,Hiroki Akutsu,Lee Martin,Toby J. Blundell,Pierre Le Maguere,Scott S. TurnerDalton Trans., 2021,50, 11843-11851 10.1039/D1DT01743H
- [10] Excimer–monomer switch: a reaction-based approach for selective detection of fluoride? Qiao Song,Angela Bamesberger,Lingyun Yang,Haley Houtwed,Haishi CaoAnalyst, 2014,139, 3588-3592 10.1039/C4AN00522H
Journal Name：Organic & Biomolecular Chemistry
research_products
-
CAS no.: 89640-58-4
![N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide](https://ossimg.kuujia.com/scimg/1444500/1444113-98-7x500.png)
![1,2,3,4,5,6-Hexahydro-[2,3]bipyridinyl-6-ol](https://ossimg.kuujia.com/scimg/1271000/1270529-38-8x500.png)
![2,2-Difluoro-3-[methyl(2-methylbutyl)amino]propanoic acid](https://ossimg.kuujia.com/scimg/2138500/2138166-62-6x500.png)
![2-(1H-indol-3-yl)-N-{[6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}acetamide](https://ossimg.kuujia.com/scimg/2034500/2034271-14-0x500.png)