关键词：
Chemical;Rice bacterial brown stripe pathogen;Gene expression;Action mode
摘要：
Thiamin diphosphate (ThDP) analogs have been designed and synthesized based on the ThDP binding site of the pyruvate dehydrogenase multienzyme complex E1 of Escherichia coli. This study investigated the effect of 66 novel ThDP analogs on rice bacterial brown stripe pathogen Acidovorax avenae subsp. avenae strain RS-1. Results indicated that three of the 66 ThDP analogs (designated as 20, 21 and 53) significantly inhibited the in vitro growth of strain RS-1. However, no obvious cell lysis and destruction was found for this rice pathogenic bacterium, which were supported by morphological evidence of transmission electron microscope. In contrast, the three ThDP analogs significantly reduced biofilm formation and the activity of the pyruvate dehydrogenase of strain RS-1. Furthermore, the differential expression of ThDP target gene and 20 secretion system related genes were revealed by using quantitative real-time PCR. Among these, the expressions of ThDP target gene and VgrG-5 under the treatment of ThDP 20 were strongly induced compared to the control, which indicated that the antibacterial mechanism of ThDP analogs may be mainly due to the changed expression of ThDP target gene and secretion system related genes rather than causing damage to cell membrane. Taken together, the application of synthesized ThDP analogs might be a tractable strategy to overcome the pathogen of rice bacterial brown stripe.
摘要：
By targeting the thiamin diphosphate (ThDP) binding site of Escherichia coli (E. coli) pyruvate dehydrogenase multienzyme complex E1 (PDHc E1), a series of novel 'open-chain' classes of ThDP analogs A, B, and C with N-acylhydrazone moieties was designed and synthesized to explore their activities against E. coli PHDc E1 in vitro and their inhibitory activity against microbial diseases were further evaluated in vivo. As a result, A1-23 exhibited moderate to potent inhibitory activities against E. coli PDHc E1 (IC50 = 0.15-23.55 mu M). The potent inhibitors A13, A14, A15, C2, had strong inhibitory activities with IC50 values of 0.60, 0.15, 0.39 and 0.34 mu M against E. coli PDHc E1 and with good enzyme-selective inhibition between microorganisms and mammals. Especially, the most powerful inhibitor A14 could 99.37% control Xanthimonas oryzae pv. Oryzae. Furthermore, the binding features of compound A14 within E. coli PDHc E1 were investigated to provide useful insights for the further construction of new inhibitor by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that A14 had most powerful inhibition against E. coli PDHc E1 due to the establishment of stronger interaction with Glu571, Met194, Glu522, Leu264 and Phe602 at active site of E. coli PDHc E1. It could be used as a lead compound for further optimization, and may have potential as a new microbicide. (C) 2017 Elsevier Ltd. All rights reserved.
摘要：
α-(Substituted phenoxyacetoxy) alkylphosphonates containing one chiral carbon atom have been demonstrated to be PDHc inhibitor with good herbicidal activity and some of them could be used as potential herbicide. In order to determine any difference in herbicidal activities between (R) and (S) isomers, the synthetic method of optically active substituted phenylalkylphosphonates IB were explored. A highly practical, enantioselective hydrophosphonylation was developed to prepare optically active O,O-dimethyl α-hydroxyalkylphosphonates 3 as key intermediate by asymmetric addition reaction of dimethylphosphite 1 and several kinds of aldehydes 2 using tridentate Schiff base Al(III) complexes as catalysts. A series of novel O,O-dimethyl α-(substituted phenoxyacetoxy)(substituted phenyl)methylphosphonates IB including (R) and (S) enantiomers were further synthesized with excellent enantioselectivity (95–99% ee) by the condensation of optically active α-hydroxyl (substituted phenyl)methylphosphonates 3 and substituted phenoxyacetyl chlorides 4. The herbicidal activities of title compound IB including their racemates, (R) and (S) enantiomers were evaluated in greenhouse for post-emergence application. All compounds IB showed significant inhibitory activity against dicotyledonous plants. A difference in herbicidal effect among racemate, (R) and (S) enantiomers were observed. Especially IB7 and IB10 showed obvious chiral selectivity in inhibitory activity against chickweed. (S)-IB7 with ED50 of 22.8 g ai/ha was found to be most effective enantiomer against chickweed and its inhibitory activity was 8.17 times higher than (R)-IB7. (S)-IB7 as potential herbicide would be effective at lower rates than (R)-IB7 or (rac)-IB7.
摘要：
Based on our previous work on the structural modification of the lead compound I, three series of novel fluorine-containing phosphonates derivatives (II, III and IV) were designed and synthesized. Their post-emergence herbicidal activities against some species of weeds were evaluated in a green house. The compounds II were synthesized by introducing of two methylene into the structure I. Compared with the commercial herbicidal clacyfos, compounds II showed moderate herbicidal activity with 60–85% inhibition effect against chingma abutilon (Abutilon theophrasti), common amaranth (Amaranthus retroflexus) and white eclipta (Eclipta prostrate) at a rate of 150 g ai/ha. The compounds III were designed by introducing open-chain phosphonates, which displayed notable herbicidal activity. Especially, the compounds III-1–III-4, III-6, III-8, III-11 and III-12 exhibited significant herbicidal activity (80–100%) comparing to the clacyfos against all tested broadleaf weeds, while compounds IV with five carbon atoms in the carboxylic acid chain were inactive against all of the tested weeds. Structure-activity relationship analyses indicated that the length of the carbon chain had a great effect on the herbicidal activity. Furthermore, a broad spectrum test confirmed that compounds III-4 and III-8 were comparable with glyphosate against all of the tested weeds at a rate of 75 g ai/ha.
期刊：
Chinese Journal of Structural Chemistry,2016年35(6):857-862 ISSN：0254-5861
通讯作者：
Peng Hao
作者机构：
[Peng Hao] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.
通讯机构：
[Peng Hao] C;Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
A new crystal of (E)-2-(2,4-dichlorophenoxy)-l-(5,5-dimethyl-2-oxido-1,3.2-dioxa-phosphinan-2-yl)vinyl 2-(2,4-dichlorophenoxy)acetate has been determined by single-crystal X-ray diffraction. The compound crystallizes in triclinic, space group P1 with a = 7.9393(17),b = 11.974(3) A,c = 13.532(3) A, a = 90.937(4),β=101.998(3),y = 101.363(4)°,V= 1231.5(5) A~3, D_c =1.500 Mg/m~3, Z = 2,F(000) = 568 and μ = 0.585 mm~(-1). The molecular packing in the crystal is the result of C(10)-H(10)...O(5) hydrogen bond, as well as weak π-π stacking interactions. The herbicidal activity results indicated that the title compound 3 showed 80~100% inhibitory activities against all of the tested weeds at a dosage of 150 g-ai/ha.
