摘要:
Three groups of pyrrolidinium headgroup-based gemini surfactants of 1,1'-(propane-1,3-diyl) bis(1-alkyl pyrrolidinium) bromide, in categories of symmetric CmC3CmPB (m = 10, 12, 14), dissymmetric CmC3C14PB (m = 10, 12, 14) and CmC3CnPB (m = 8, 10, 12, m + n = 24) surfactants, are studied using equilibrium surface tension, conductivity, fluorescence, and NMR techniques. The importance of the dissymmetry on the micellization has been revealed in detail. The increase in the hydrophobic chain length m for CmC3CmPB and CmC3C14PB or in the dissymmetry (n/m) for CmC3CnPB can strengthen the aggregation ability and surface activity of the surfactants significantly, i.e., a lower critical micelle concentration (cmc) and a lower surface tension at cmc (gamma(cmc)). However, the aggregation number at cmc (N*) obeys the opposite variation tendency and it becomes smaller upon increasing m or n/m, due to the formation of premicelles. Thermodynamic results reveal that the contribution of enthalpy (Delta H-m(0)) to the Gibbs free energy (Delta G(m)(0)) is strengthened by increasing m or n/m during the spontaneous micellization process. Moreover, H-1 NMR results confirm the microenvironment change of the surfactants from polar water to micelles during the micellization, and 2D Noesy NMR spectra suggest that the methylene groups in the ring should adopt a conformation toward the nonpolar micellar core rather than in the polar water.
通讯机构:
[Hao, Ge-Fei] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
摘要:
Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation.
摘要:
BACKGROUNDPyridalyl is a highly active insecticide against lepidopterous larvae, with a novel chemical structure not related to any other existing insecticide. To discover new pyridalyl analogues with high activity against resistant pests, a series of 1,1-dichloropropene derivatives bearing structurally diverse substituted heterocycle rings in place of the pyridine ring of pyridalyl were designed and synthesised. RESULTSAll of the title compounds were confirmed by H-1 NMR, C-13 NMR and high-resolution mass spectra. Two representative compounds (Ic and IIa) were further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed good insecticidal activity against Prodenia litura. Further determination of LD50 values and field trials identified compound IIa as the most promising candidate, which produced a much better 14 day control effect against diamondback moths and longer duration of efficacy than pyridalyl, indicating its potential for further development as a new insecticide for the control of lepidopteran insects. CONCLUSIONCompound IIa has great potential for further development as a new insecticide for the control of lepidopteran insects. (c) 2014 Society of Chemical Industry
期刊:
Pest Management Science,2015年71(8):1122-1132 ISSN:1526-498X
通讯作者:
Yang, Wen-Chao
作者机构:
[Yang, Guang-Fu; Yang, Wen-Chao; Ming, Ze-Zhong; Chen, Tao; Wang, Da-Wei; Lin, Hong-Yan; Cao, Run-Jie; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin, Peoples R China.;[Yang, Wen-Chao] Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
通讯机构:
[Yang, Wen-Chao] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词:
herbicide;4-hydroxyphenylpyruvate dioxygenase;quinazoline-2;4-dione;structure-activity relationship;weed control
摘要:
BACKGROUND4-Hydroxyphenylpyruvate dioxygenase (HPPD) (EC 1.13.11.27) has been identified as one of the most promising target sites for herbicide discovery. To discover novel HPPD inhibitors with high herbicidal activity and improved crop selectivity, a series of novel triketone-containing quinazoline-2,4-dione derivatives possessing a variety of substituents at the N-1 position of the quinazoline-2,4-dione ring were designed and synthesised. RESULTSThe results of in vitro tests and greenhouse experiments indicated that some analogues showed good HPPD inhibitory activity, with promising broad-spectrum herbicidal activity at a rate of 150g AI ha(-1). Most surprisingly, compound 11h, 1-ethyl-6-(2-hydroxy-6-oxocyclohex-1-enecarbonyl)-3-(o-tolyl)quinazoline-2,4(1H,3H)-dione, showed the highest HPPD inhibition activity, with a K-i value of 0.005 M, about 2 times more potent than mesotrione (K-i=0.013 M). Further greenhouse experiments indicated that compounds 11d and 11h displayed strong and broad-spectrum post-emergent herbicidal activity even at a dosage as low as 37.5g AI ha(-1), which was superior to mesotrione. More importantly, compounds 11d and 11h were safe for maize at a rate of 150g AI ha(-1), and compound 11d was safe for wheat as well. CONCLUSIONThe present work indicated that the triketone-containing quinazoline-2,4-dione motif could be a potential lead structure for further development of novel herbicides. (c) 2014 Society of Chemical Industry
通讯机构:
[Wang Dawei] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
关键词:
对羟苯基丙酮酸双氧化酶;抑制剂;喹唑啉二酮;除草剂;先导化合物
摘要:
对羟苯基丙酮酸双氧化酶(EC 1.13.11.27,HPPD)是一个重要的除草剂作用靶标.为了寻找具有高效除草活性的新型HPPD抑制剂,在前期研究的基础上设计合成了24个含有喹唑啉二酮结构的三酮类化合物9a~9x.所合成的化合物均经过~1H NMR,~(13)C NMR和HRMS的表征.以来源于拟南芥的HPPD(At HPPD)为测试对象进行酶抑制活性筛选,结果表明所合成的大部分化合物对At HPPD均表现出了较好的抑制效果,其中化合物9i的K_i值为0.005μmol/L,显著优于商品化对照药剂硝磺草酮(K_i=0.013μmol/L).进一步温室盆栽筛选结果表明,多数化合物在150 g ai/ha的剂量下对六种供试杂草中的至少一种表现出80%以上的防效,特别是化合物9g在37.5 g ai/ha的低剂量下对所测试的六种杂草中的四种仍表现出了大于85%的抑制效果,同时9g在150 g ai/ha的剂量下对水稻和小麦均表现出了很好的作物安全性,可以作为先导化合物供进一步深入研究.
通讯机构:
[Wu, Qiong-You] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要:
Respiratory chain succinate-ubiquinone oxidoreductase (SQR or complex II) and ubihydroquinonecytochrome (cyt) c oxidoreductase (cyt bc(1) or complex III) have been demonstrated as the promising targets of numerous antibiotics and fungicides. As a continuation of our research work on the development of new fungicides, a series of 1,2,4-triazole-1,3-disulfonamide derivatives with dual functions targeting both SQR and cyt bc(1) were designed and synthesized by coupling diverse diphenyl ether moieties with triazolesulfonamide units. These newly synthesized compounds were characterized by elemental analyses, H-1 NMR and ESI-MS spectrometry. The in vitro assay indicated that most of the synthesized compounds displayed good inhibition against porcine succinate-cytochrome reductase (SCR) with IC50 values ranging from 3.2 to 81.8 mu M, revealing much higher activity than that of the commercial control amisulbrom whose IC50 value is 93.0 mu M. Further evaluation against the respective SQR and cyt bc(1) indicated that most compounds exhibited SQR-inhibiting activity as well as cyt bc(1)-inhibiting activity, but the inhibition potency against SQR is much higher than that against cyt bc(1), showing that the SCR inhibition might be contributed greatly by the SQR inhibition. The further antibacterial evaluation against Xanthomonas oryzae pv. oryzae revealed that four compounds showed excellent potency at the concentration of 20 mu g mL(-1). In particular, compounds 6h and 6j exhibited much better antibacterial activity than the commercial control bismerthiazol in terms of their EC50. Impressively, 6j has an EC90 of 33.62 mu g mL(-1), more than 10-fold higher than that of bismerthiazol.
作者机构:
[Yang, Guang-Fu; Yang, Sheng-Gang; Tu, Wen-Long; Huang, Wei; Li, Hui; Shen, Yan-Qing; Hao, Ge-Fei] Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;[Yang, Guang-Fu] Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300072, Peoples R China.;[Wu, Jia-Wei; Wang, Le] Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, MOE Key Lab Prot Sci, Beijing 100084, Peoples R China.;[Huang, Li-Shar; Berry, Edward A.] SUNY Upstate Med Univ, Dept Biochem & Mol Biol, Syracuse, NY 13210 USA.
通讯机构:
[Hao, Ge-Fei] C;Cent China Normal Univ, Coll Chem, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要:
Hit to lead (H2L) optimization is a key step for drug and agrochemical discovery. A critical challenge for H2L optimization is the low efficiency due to the lack of predictive method with high accuracy. We described a new computational method called Computational Substitution Optimization (CSO) that has allowed us to rapidly identify compounds with cytochrome bc1 complex inhibitory activity in the nanomolar and subnanomolar range. The comprehensively optimized candidate has proved to be a slow binding inhibitor of bc1 complex, ~73-fold more potent (Ki = 4.1 nM) than the best commercial fungicide azoxystrobin (AZ; Ki = 297.6 nM) and shows excellent in vivo fungicidal activity against downy mildew and powdery mildew disease. The excellent correlation between experimental and calculated binding free-energy shifts together with further crystallographic analysis confirmed the prediction accuracy of CSO method. To the best of our knowledge, CSO is a new computational approach to substitution-scanning mutagenesis of ligand and could be used as a general strategy of H2L optimisation in drug and agrochemical design.
摘要:
As an important fragment and synthetic intermediate, functionalized 6-arylsalicylate substructure widely exist in pharmacologically relevant natural products and bioactive compounds. In our recent works, we discovered two highly potent inhibitors for combating mutants of acetohydroxyacid synthase (AHAS), an important target for herbicide discovery. These two inhibitors contain 6-arylsalicylate skeleton. Previously, we have explored a new method to synthesize position-6 aryl substituted salicylic acid fragment. However, this method failed to synthesize 4-methyl-6-aryl salicylic acids. Herein, we developed a new efficient method for the synthesis of functionalized 4-methyl-6-bulkyarylsalicylates via a microwave-promoted Suzuki cross-coupling. This method has obvious advantages, such as a wide range of substrates, smooth and rapid reaction, moderate to excellent yields. Due to its superiority to the traditional available methods, this protocol could be utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.