Jiwen Zhang

Synthesis and Insecticidal Activities of New Ester-Derivatives of Celangulin-V

In order to develop new biorational pesticides, ten new 6-substituted ester derivatives of Celangulin-V were designed and synthesized. The structures of the new derivatives were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS spectral analysis. Insecticidal activities of these compounds were tested against the third-instar larvae of Mythimna separata. Two derivatives (1.1, 1.2) showed higher insecticidal activities than Celangulin-V, with mortality of 75.0% and 83.3%, respectively. While four compounds (1.3, 1.4, 1.7, 1.8) denoted lower insecticidal activities, the others (1.5, 1.6, 1.9, 1.10) revealed no activities at a concentration of 10 mg.mL−1. The results suggest that C-6 substitutions of Celangulin-V are very important in determining the insecticidal activities of its ester-derivatives. That the acetyl (1.1) and propionyl (1.2) derivatives possessed much higher insecticidal activities than Celangulin-V itself supported the view that Celangulin-V has the potential to be a lead structure of semi-synthetic green insecticides.

Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of β-Dihydroagarofuran Derivatives

The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 β-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT-135°, IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 μg/g, respectively, which were much lower than that of celangulin-V (327.6 μg/g). These results illustrated that β-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development.

Synthesis and Antibacterial Activities of Yanglingmycin Analogues

The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with minimum inhibitory concentration (MIC) values ranging from 3.91 to 15.62u2009µg/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides.

Design, synthesis and cytotoxic activity of a novel series of steroidal phenylpyrazoles

Thirty novel steroidal pyrazole derivatives were designed and synthesized via a highly efficient route from pregnenolone (1) as starting material. The key intermediates 3a-c were obtained under Vilsmeier conditions, and the subsequent hydrolysis, acetylation or Borch reduction afforded thirty target compounds. These compounds were mainly characterized by (1)H NMR, (13)C NMR, DEPT135°. The structure of compound 3a was also confirmed by X-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the SRB method against four cancer cell lines, including A549, Hela, MCF-7 and HepG2, and the results indicated that compounds 5a, 6a, 7a and 8a exhibited significant cytotoxicity with IC50 values ranging from 0.91 to 5.44 μM. Most importantly, compound 5a exhibited excellent cytotoxicity against A549 with an IC50 value of 0.91 μM. On the basis of our research the structure-activity relationships (SAR) of these compounds were discussed. This work provides some important hints for further structural modification of steroids towards developing novel and highly effective anticancer drugs.

Design and Synthesis of New 2-Aryl-4,5-Dihydro-thiazole Analogues: In Vitro Antibacterial Activities and Preliminary Mechanism of Action

Sixty 2-aryl-4,5-dihydrothiazoles were designed and synthesized in yields ranging from 64% to 89% from cysteine and substituted-benzonitriles via a novel metal- and catalyst-free method. The structures of the title compounds were confirmed mainly by NMR spectral data analysis. Antibacterial activity assays showed that the compounds (S)-2-(2′-hydroxyphenyl)-4-hydroxy-methyl-4,5-dihydrothiazole (7h) and (R)-2-(2′-hydroxyphenyl)-4-hydroxymethyl-4,5-dihydro-thiazole (7h′) exhibited significant inhibition against Ralstonia solanacearum, Pseudomonas syringae pv. actinidiae, Bacillus subtilis and Bacillus cereus, with minimum inhibitory concentrations (MICs) ranging from 3.91 to 31.24 μg·mL−1. The effect of substituents showed that not only electron-withdrawing groups, but also electron-donating groups could abolish the antibacterial activities unless a 2′-hydroxy group was introduced on the 2-aryl substituent of the 4,5-dihydrothiazole analogues. The results of scanning electron microscope (SEM) and fatty acid exposure experiments indicated that these antibacterial compounds influence fatty acid synthesis in the tested bacteria.

Synthesis and insecticidal activity of β-dihydroagarofuran ether analogues

BACKGROUNDn1β, 2β, 4α, 6α, 8β, 9α, 12-hepthydroxyl-β-dihydroagarofuran is the main skeleton of β-dihydroagarofuran sesquiterpenoids, which exhibit excellent insecticidal activity. To study further the structure-activity relationship of β-dihydroagarofuran sesquiterpenoids towards finding novel botanical pesticides, two series of new structurally modified ether analogues were designed and synthesised, and their insecticidal activities were evaluated.nnnRESULTSnTwenty-two ether derivatives were synthesised using 1β, 2β, 4α, 6α, 8β, 9α, 12-hepthydroxyl-β-dihydroagarofuran as starting material. Bioassay results indicated that most of the derivatives, particularly compounds 5.1.2, 5.1.3, 5.1.7, 5.2.3, 5.2.6 and 5.2.7, exhibited significant insecticidal activity against the third-instar larvae of the oriental armyworm Mythimna separata. Most importantly, compound 5.2.7 showed the lowest LD50 value of 29.2 µg g(-1) among these synthesised compounds, which provides some important hints for further design, synthesis and structural modification of β-dihydroagarofuran sesquiterpenoids towards developing novel botanical insecticides.nnnCONCLUSIONnThe structure-activity relationship illustrated that the moiety at the 1-position affected the insecticidal activity significantly, and that specifically the derivatives with two or three carbon atoms at the 1-position showed promising insecticidal activity, with mortality over 60%, while those with o-F-Bn and p-F-Bn at the 6-position showed similar activity.

Efficient Synthesis and Antibacterial Evaluation of (±)-Yanglingmycin and Its Analogues

An efficient synthetic route was developed for the large-scale preparation of (±)-Yanglingmycin and its analogues. Three series of derivatives of (±)-Yanglingmycin were synthesized and the structures of all compounds were elucidated by analyses of NMR and ESI-MS spectra data. Moreover, their antibacterial activities against seven species of bacteria were systematically evaluated by the micro-broth dilution method, most of which displayed considerable activity. It was worth noting that compounds 5b, 5c, 5d, 6g, and 7 were found to be the most promising leading candidates, with peak MIC values of 0.98 μg·mL−1 for Bacillus subtilis, which is superior to positive controls (MIC = 3.91 μg·mL−1). The above results might lay the firm foundation for the design and synthesis of novel antibacterial drugs based on (±)-Yanglingmycin.

Synthesis and Larvicidal Activity against Culex pipiens pallens of New Triazole Derivatives of Phrymarolin from Phryma leptostachya L.

Twelve new triazole derivatives of Phrymarolin were prepared from Phrymarolin I and the structures of all the derivatives were fully characterized by 1H-NMR, 13C-NMR and MS spectral data analyses. Larvicidal activities against 4rd instar larvae of Culex pipiens pallens of these Phrymarolin analogues were assayed. Although the triazole derivatives of Phrymarolin showed certain larvicidal activity, they showed lower activity than Phrymarolin I. The typical non-natural groups triazole substituents reduced the larvicidal activity of Phrymarolin derivatives.

Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

Celangulin V (CV), one of dihydroagarofuran sesquiterpene polyesters isolated from Chinese bittersweet (Celastrus angulatus Maxim), is famous natural botanical insecticide. Decades of research suggests that is displays excellent insecticidal activity against some insects, such as Mythimna separata Walker. Recently, it has been validated that the H subunit of V-ATPase is one of the target proteins of the insecticidal dihydroagarofuran sesquiterpene polyesters. As a continuation of the development of new pesticides from these natural products, a series of β-dihydroagarofuran derivatives have been designed and synthesized. The compound JW-3, an insecticidal derivative of CV with a p-fluorobenzyl group, exhibits higher insecticidal activity than CV. In this study, the potential inhibitory effect aused by the interaction of JW-3 with the H subunit of V-ATPase c was verified by confirmatory experiments at the molecular level. Both spectroscopic techniques and isothermal titration calorimetry measurements showed the binding of JW-3 to the subunit H of V-ATPase was specific and spontaneous. In addition, the possible mechanism of action of the compound was discussed. Docking results indicated compound JW-3 could bind well in ‘the interdomain cleft’ of the V-ATPase subunit H by the hydrogen bonding and make conformation of the ligand–protein complex become more stable. All results are the further validations of the hypothesis, that the target protein of insecticidal dihydroagarofuran sesquiterpene polyesters and their β-dihydroagarofuran derivatives is the subunit H of V-ATPase. The results also provide new ideas for developing pesticides acting on V-ATPase of insects.

Composition, in vitro antioxidant and antimicrobial activity of the essential oils from Artemisia lavandulaefolia DC.

The essential oils from the aerial parts ofxa0Artemisia lavandulaefoliaxa0DC., a traditional medicinal plant growing in China, were obtained by hydro distillation and analyzed byxa0gas chromatograph and mass spectrometerxa0xa0(GC-MS). Fifteen monoterpenes, six sesquiterpenes, three monoterpenoid acetates with two aromatic compounds and two others were identified among twenty-eight compounds, representing 99.69% of the total oils. Eucalyptol (20.62%), Borneol (15.32%), Eudesm-7(11)-en-4-ol (13.81%), Sabinol (9.75%), β-Terpineol (6.86%), trans-Pinocarvyl acetate (6.13%) and α-Terpineol (5.35%) were the major seven compounds in the essential oils. The essential oils displayed significantxa0in vitroxa0antimicrobial activities againstBacillus subtilus,xa0Pseudomonas aeruginosa,xa0Bacillus cereus1xa0andxa0Staphylococcus aureuswith minimum inhibitory concentration values range of 125 to 250 μg/ml. Thexa0in vitroxa0antioxidant activities were assessed by DPPH radical scavenging and inhibition of lipid peroxidation methods. The oils showed a remarkable free radical scavenging activities, as evidenced by the low IC50xa0value for DPPH radical (275.7 μg/ml) and inhibition of lipid peroxidation (induced by FeSO4, H2O2xa0and CCl4) with IC50xa0values of 393.6, 562.8 and 297.2 μg/ml, respectively. n n xa0 n n Key words:xa0Artemisia lavandulaefoliaxa0DC., antioxidant activities, antimicrobial activities, essential oils.