Design, Synthesis and Bioactivity of Novel Pyrimidine Sulfonate Esters Containing Thioether Moiety.

Pesticides play an important role in crop disease and pest control. However, their irrational use leads to the emergence of drug resistance. Therefore, it is necessary to search for new pesticide-lead compounds with new structures. We designed and synthesized 33 novel pyrimidine derivatives containing sulfonate groups and evaluated their antibacterial and insecticidal activities. Results: Most of the synthesized compounds showed good antibacterial activity against Xanthomonas oryzae pv. Oryzae (Xoo), Xanthomonas axonopodis pv. Citri (Xac), Pseudomonas syringae pv. actinidiae (Psa) and Ralstonia solanacearum (Rs), and certain insecticidal activity. A5, A31 and A33 showed strong antibacterial activity against Xoo, with EC50 values of 4.24, 6.77 and 9.35 µg/mL, respectively. Compounds A1, A3, A5 and A33 showed remarkable activity against Xac (EC50 was 79.02, 82.28, 70.80 and 44.11 µg/mL, respectively). In addition, A5 could significantly improve the defense enzyme (superoxide dismutase, peroxidase, phenylalanine ammonia-lyase and catalase) activity of plants against pathogens and thus improve the disease resistance of plants. Moreover, a few compounds also showed good insecticidal activity against Plutella xylostella and Myzus persicae. The results of this study provide insight into the development of new broad-spectrum pesticides.

Smart Synthesis of Trimethyl Ethoxysilane (TMS) Functionalized Core-Shell Magnetic Nanosorbents Fe3O4@SiO2: Process Optimization and Application for Extraction of Pesticides.

In the current study, a smart approach for synthesizing trimethyl ethoxysilane-decorated magnetic-core silica-nanoparticles (TMS-mcSNPs) and its effectiveness as nanosorbents have been exploited. While the magnetite core was synthesized using the modified Mössbauer method, Stöber method was employed to coat the magnetic particles. The objective of this work is to maximize the magnetic properties and to minimize both particle size (PS) and particle size distribution (PSD). Using a full factorial design (2k-FFD), the influences of four factors on the coating process was assessed by optimizing the three responses (magnetic properties, PS, and PSD). These four factors were: (1) concentration of tetraethyl-orthosilicate (TEOS); (2) concentration of ammonia; (3) dose of magnetite (Fe3O4); and (4) addition mode. Magnetic properties were calculated as the attraction weight. Scanning electron microscopy (SEM) was used to determine PS, and standard deviation (±SD) was calculated to determine the PSD. Composite desirability function (D) was used to consolidate the multiple responses into a single performance characteristic. Pareto chart of standardized effects together with analysis of variance (ANOVA) at 95.0 confidence interval (CI) were used to determine statistically significant variable(s). Trimethyl ethoxysilane-functionalized mcSNPs were further applied as nanosorbents for magnetic solid phase extraction (TMS-MSPE) of organophosphorus and carbamate pesticides.

A sodium alginate-based nano-pesticide delivery system for enhanced in vitro photostability and insecticidal efficacy of phloxine B.

To improve in vitro photostability and enhance insecticidal activity, a novel esterase/glutathione (GSH) responsive photoactivated nano-pesticide delivery system was synthesized by conjugation of photoactivated pesticide phloxine B(PB) to sodium alginate (SA) via esterase/GSH sensitive phenolic ester bond followed by ultrasonic dispersion. The system was stable in PBS (pH 7.4) and could protect effectively the conjugated PB from in vitro photodegradation because of aggregation-caused quenching effect, whose maximum photodegradation rate did not exceed 10 % after 270 min illumination. However, upon exposure to esterase-6 or GSH stimulus, high photoactivity was observed due to the destruction of the system and accompanied by PB release. The combined stimulation could trigger more PB release than any single stimulus and thus resulting in a higher photoactivity. Compared with free PB, The system showed a higher phototoxicity on Sf9 insect cells and the in vitro light exposure had little influence on the phototoxicity.

Visible-Light-Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides.

Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.

Investigation of Novel Pesticides with Insecticidal and Antifungal Activities: Design, Synthesis and SAR Studies of Benzoylpyrimidinylurea Derivatives.

In order to find pesticides with insecticidal and antifungal activities, a series of novel benzoyl pyrimidinylurea derivatives were designed and synthesized. All target compounds were identified by ¹H-NMR spectroscopy and HRMS. Insecticidal and antifungal activity of these compounds were evaluated and the structure-activity relationships (SAR) were clearly and comprehensively illustrated. Compound 7, with low toxicity to zebrafish (LC50 = 378.387 µg mL-1) showed 100% inhibition against mosquito (Culex pipiens pallens) at 0.25 µg mL-1. Both compounds 19 and 25 exhibited broad-spectrum fungicidal activity (>50% inhibitory activities against 13 phytopathogenic fungi), which were better than those of the commercial pesticide pyrimethanil (>50% inhibitory activities against eight phytopathogenic fungi). Furthermore, compounds 19 and 25 exhibited protective activity against Sclerotinia sclerotiorum on leaves of Brassica oleracea L. during in vivo experiments.

Design, Synthesis, and Biological Activity of ß-Carboline Analogues Containing Hydantoin, Thiohydantoin, and Urea Moieties.

A series of novel ß-carboline derivatives was designed by combining the anti-tobacco mosaic virus (TMV) lead compound tetrahydro-ß-carboline ester with the hydantoin, thiohydantoin, and urea motifs. These derivatives were synthesized from tetrahydro-ß-carboline ester via a structural diversity-oriented synthesis in one step, and their biological activities were evaluated. Most of the derivatives exhibited anti-TMV activity higher than that of commercial plant virucide ribavirin, such as compounds 2, 4, 5, 7, 9, 15, 16, 19, and 21. Compared with the lead compounds, some of these derivatives showed good insecticidal activity against Plutella xylostella and Culex pipiens pallens. At the same time, these derivatives also showed broad-spectrum fungicidal activity. The systematic study provides strong evidence that the hydantoin, thiohydantoin, and urea motifs of these molecules can improve and modulate the activities of the analogues of natural products.

[Avermectin, from winning the Nobel Prize to "innovation in China"].

The uprise of the superpower nations is always accompanied by the breakthrough and advances of technologies and innovations in the history. Natural products play very important role in human health, such as anticancer molecular taxol, anti-infection drug artemisinin that save a lot of lives, metabolic disease treatment, nutrition and health care. However, more has never been explored. With the 2015 Nobel Prize in Physiology or Medicine awarded to William C. Campbell, Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin respectively, the second "Golden age" in the development of natural product is dawning. China is a "world factory" and natural drugs-rich country, but how to upgrade and advance the industry and realize the China dream? Avermectins, produced by Streptomyces avermitilis, are pesticide with high efficiency and low levels of side effects. However, the low producer and expensive development pattern of high consumption, high contamination is not sustainable. Solving the problem, increasing the production and utilization of raw material, reducing the energy consumption and cost of production, decreasing environmental pollution are key to transform China into a power house. In this paper, we case-study avermectins to review the industry development driven by fundamental research. Institute of Microbiology, Chinese Academy.of Sciences increased the production of avermectin 1000 folds to 9 g/L, which out licensed to new Veyong biochemical Ltd and avermectin Coalitions. As a result, Merck Sharp and Dohme ceased the manufacture of avermectins. The success also shed lights on the improvement of other natural product drugs in China.

Synthesis and insecticidal activities of novel pyrazole oxime ether derivatives with different substituted pyridyl rings.

BACKGROUND: Pyrazole oxime ether derivatives with different substituted pyridyl rings represent new types of compounds that possess good insecticidal and acarcidal activity against Aphis laburni Kaltenbach and Tetranychus cinnabarinus. RESULTS: In total, 82 novel pyrazole oxime ether derivatives were synthesized and identified by (1) H NMR, elemental analysis or high-resolution mass spectrometry, and their insecticidal and acarcidal activities were tested against A. laburni Kaltenbach and T. cinnabarinus. Bioassays showed that at a 200 mg L(-1) dosage, one-third of the compounds displayed high insecticidal activity against A. laburni Kaltenbach (> 90%), whereas most of of the compound II series exhibited excellent acarcidal activity against T. cinnabarinus (> 92%). Most compound II series exhibited good activity in both insecticidal and acarcidal tests. In addition, at a low concentration of 10 mg L(-1) , the insecticidal activity of compounds IB9 and IE4 exceeded 90%, and the acarcidal activity of compounds IIB1 and IIB2 was ≥ 95%. CONCLUSION: Structure-activity relationships were also examined. Results suggested that the tert-butoxycarbonyl group, as well as the position between tert-butoxycarbonyl and the atom N of the pyridyl ring, were essential to obtaining the acarcidal activity of the title compounds.

Review of advances in the thin layer chromatography of pesticides: 2010-2012.

Techniques and applications of thin layer chromatography (planar chromatography) for the separation, detection, qualitative and quantitative determination, and preparative isolation of pesticides and their metabolites and some related pollutants are reviewed for the period from November 1, 2010 to November 1, 2012. Analyses are described for a variety of samples types and pesticide classes. In addition to references on residue analysis, studies such as pesticide structure - retention relationships, identification and characterization of natural and synthesized pesticides, metabolism, degradation, mobility, lipophilicity, and mechanism of action are covered.

Synthesis of nalidixic acid based hydrazones as novel pesticides.

Thirty-one substituted hydrazones of nalidixic acid hydrazide were synthesized and characterized by spectral techniques. These compounds were evaluated for various biological activities, namely, fungicidal, insecticidal, and nitrification inhibitory activities. The antifungal activity was evaluated against five pathogenic fungi, namely, Rhizoctonia bataticola , Sclerotium rolfsii , Rhizoctonia solani , Fusarium oxysporum , and Alternaria porii . They showed maximum inihibition against A. porii with ED(50) = 34.2-151.3 microg/mL. The activity was comparable to that of a commercial fungicide, hexaconazole (ED(50) = 25.4 microg/mL). They were also screened for insecticidal activity against third-instar larvae of Spodoptera litura and adults of Callosobruchus maculatus and Tribollium castaneum . Most of them showed 70-100% mortality against S. litura through feeding method at 0.1% dose. These compounds were not found to be effective nitrification inhibitors.

Preparation and preliminary biological screening of cholic acid-juvenoid conjugates.

Steroidal compounds have been utilized as carriers and for modification of physico-chemical properties of model biologically active secondary alcohols - juvenoids. Juvenoids are juvenile hormone analogues - environmentally safe insecticides, possessing significant biological activity towards different arthropods groups in focus on insect pest species. Structure modification of juvenoids plays important role to control the rate of liberation and decomposition of juvenoid in digestive system and can also play important role in the mode of action towards selected insect. This study presents an approach to the synthesis of steroidal monomers and dimers carrying one and two molecules of a juvenoid in their structures. The prepared compounds were tested for their inhibition activity on reproduction of the blowfly Neobellieria (Sarcophaga) bullata. These steroid-juvenoid conjugates showed promising possibilities in synthesis of new unique biochemical insecticides. Preliminary biological test results of prepared compounds are presented.

Novel antiviral activity of dialdehyde starch

A significant effort worldwide is being directed toward development of novel biocides against drug-resistant bacterial and viruses because of the significant potential human infection risks in the general population. We report here the discovery of a strong antiviral biocide, dialdheyde starch (DAS). Antiviral tests were carried out against three non-envelop viruses, including two bacterial viruses MS2 and PRD1, and one human virus Poliovirus. Dialdehyde starch aqueous suspensions were effective biocides against these three test viruses in a 1 hr exposure test. The antiviral activity was significantly enhanced in a four-hour exposure test, with maximum seven orders of magnitude reductions against MS2 and PRD1, and four-order reduction against Poliovirus. The antiviral activity of dialdehyde starch was found to be pH dependent, being more active in alkaline and acidic conditions than in neutral conditions.

Synthetic antimicrobial peptides as agricultural pesticides for plant-disease control.

There is a need of antimicrobial compounds in agriculture for plant-disease control, with low toxicity and reduced negative environmental impact. Antimicrobial peptides are produced by living organisms and offer strong possibilities in agriculture because new compounds can be developed based on natural structures with improved properties of activity, specificity, biodegradability, and toxicity. Design of new molecules has been achieved using combinatorial-chemistry procedures coupled to high-throughput screening systems and data processing with design-of-experiments (DOE) methodology to obtain QSAR equation models and optimized compounds. Upon selection of best candidates with low cytotoxicity and moderate stability to protease digestion, anti-infective activity has been evaluated in plant-pathogen model systems. Suitable compounds have been submitted to acute toxicity testing in higher organisms and exhibited a low toxicity profile in a mouse model. Large-scale production can be achieved by solution organic or chemoenzymatic procedures in the case of very small peptides, but, in many cases, production can be performed by biotechnological methods using genetically modified microorganisms (fermentation) or transgenic crops (plant biofactories).

Recent developments in the chemistry and in the biological applications of amidoximes.

Amidoximes are compounds bearing both a hydroxyimino and an amino group at the same carbon atom which makes them versatile building blocks for the synthesis of various heterocycles. Their importance in chemistry along with their rich biology, make amidoximes an attractive target for medicinal chemists, biochemists and biologists. Amidoximes and simple O-substituted derivatives possess very important biological activities functioning as antituberculotic, antibacterial, bacteriostatic, insecticidal, elminthicidal, antiviral, herbicidal, fungicidal, antineoplastic, antiarrythmic, antihypertensive, antihistaminic, anxiolytic-antidepressant, anti-inflammatory/antioxidant, antiaggregatory (NO donors) or plant growth regulatory agents. A number of amidoximes has already been used as drugs, or currently being in clinical trials. Their numerous pharmaceutical applications have been recently enriched, due to the fact that some mechanistic pathways, concerning their conversion to amidines, as well as their ability to release NO were clarified, giving a new insight to their mode of action and allowing the design of new therapeutic agents. The main subject of the present review paper is to highlight aspects concerning chemical and biological questions on this interesting class of compounds. Some new synthetic methodologies as well as improvements of previously reported general reactions involving amidoximes, acylated amidoximes, and amidines are presented. The biological applications of amidoximes over the end of 2006 are also extensively reviewed.

Practical, general, and systematic method for optical resolution of gem-dihalo- and monohalocyclopropanecarboxylic acids utilizing chiral 1,1'-binaphtholmonomethyl ethers: application to the synthesis of three chiral pesticides.

We performed an efficient practical and systematic optical resolution method for gem-dihalo- and monohalocyclopropanecarboxylic acids and utilizing chiral 1,1'-binaphthol monomethyl ether (R)- as the key auxiliary. Direct esterification of with (R)- gave two 1R- and 1S-diastereomeric esters with marked different R(f) values, both of which were easily separated using simple column chromatography. Monodehalogenation of separated chiral esters using t-BuMgCl and cat. Co(dppe)(2)Cl(2) gave two 1,2-trans- and 1,2-cis-diastereomers with markedly different R(f) values, both of which were similarly separated using simple column chromatography. The obtained diastereomers and were easily hydrolyzed to the desired enantiopure acids (>99%) and (>99%), respectively, with recovery of (R)-, both in good to excellent yields. Utilizing the present method, important chiral agrochemicals, carpropamid and fencyclate , were readily synthesized. Pyrethroid with three asymmetric centers was efficiently synthesized in a much better yield compared with the reported method.

Oil-in-water nanoemulsions for pesticide formulations.

A two-step process for formation of nanoemulsions in the system water/poly(oxyethylene) nonionic surfactant/methyl decanoate at 25 degrees C is described. First, all the components were mixed at a certain composition to prepare a microemulsion concentrate, which was rapidly subjected into a large dilution into water to generate an emulsion. Bluish transparent oil-in-water (O/W) nanoemulsions were formed only when the concentrate was located in the bicontinuous microemulsion (BC) or oil-in-water microemulsion (Wm) region. The existence of an optimum oil-to-surfactant ratio (R(os)) in the BC or Wm region indicates that both the phase behavior and the composition of the concentrate are important factors in nanoemulsion formation. To demonstrate potential applications of these systems, they were employed to formulate a water-insoluble pesticide, beta-cypermethrin (beta-CP). The nanoemulsion was compared with a commercial beta-CP microemulsion in terms of the stability of sprayed formulations.

Flavothionato metal complexes: implications for the use of hydroxyflavothiones as green pesticides.

Transition-metal complexes of 3-hydroxyflavothiones have been prepared and structurally characterized; the photochemical properties of these complexes have been examined and are discussed in the context of the use of these compounds as photodegradable pesticides.