804:
269:
Screening can distinguish compounds that independently induce immune responses from those that do so exclusively in the presence of some pathogen. Independent activators can be toxic to cells. Others enhance resistance only in the presence of pathogens. In 2012, five activators that protected against
233:
techniques have provided agrochemists with a method for validating potential new biochemical targets. However, genes such as avirulence genes are not essential for the organism and many potential targets lack known inhibitors. Examples of this procedure include the search for new herbicidal compounds
222:
three-dimensional (3D) shape, atom-type similarity, or 2D extended connectivity fingerprints also retrieve molecules of interest out of a database with a useful success rate. Scaffold-hopping is also efficiently achieved by virtual screening, with 2D and 3D variants providing the best results.
221:
was generated by keeping the core scaffold constant and attaching different linkers. The scores obtained from docking studies ranked these molecules. Resulting novel compounds showed a primary hit rate of 10.9%, much higher than for conventional high-throughput screening. Other tools like
65:
The rate of new molecule introductions has declined. The costs to bring a new molecule to market have risen from U.S. $ 152 million in 1995 to $ 256 million in 2005, as the number of compounds synthesized to deliver one new market introduction rose from 52,500 in 1995 to 140,000 in 2005.
119:
antimycotics or fungicides. However, the chemical environments encountered en route from the application site to the target generally require differing physicochemical properties, while the unit costs are generally much lower. Agrochemicals typically have a lower number of
156:
Structure-based design is appealing for crop researchers because of the many protein structures in the public domain, which increased from 13,600 to 92,700 between 200 and 2013. Many agrochemical crystals are now in the public domain. The structures of several interesting
124:
donors. For example, over 70% of insecticides have no hydrogen bond donor, and over 90% of herbicides have two or fewer. Desirable agrochemicals have residual activity and persistence of effect lasting up to several weeks to allow large spray intervals. The majority of
42:
Along with improved agrochemicals, seeds, fertilizers, mechanization, and precision farming, improved protection of crops from weeds, insects and other threats is highly sought. Developments over the past 1960–2013 period enabled reduced use rates, in the cases of the
216:
The likelihood of finding active analogs on the basis of a screen hit from a novel scaffold can be increased by virtual screening. Because the pharmacophore of the reference ligand is well defined, a virtual library of potential herbicidal inhibitors of the enzyme
144:
is a multidisciplinary process that is relatively new in agrochemicals. As of 2013 no products on the market were the direct result of this approach. However, discovery programs have benefited from structure-based design, including that for
197:, virtual screening and genome sequencing have helped generate drug leads. Published examples of fragment-based agrochemical design have been comparatively rare, although the method was used to generate new ACC inhibitors. A combination of
257:
Plant activators are compounds that activate a plant's immune system in response to invasion by pathogens. They play a crucial role in crop survival. Unlike pesticides, plant activators are not pathogen specific and are not affected by
234:
of the nonmevalonate, such as the discovery of new inhibitors of 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase (IspD, Enzyme
Commission (EC) number 2.7.7.60) with the best expressing a half-maximal inhibitory concentration (
249:(SHMT) inhibitors were also found. Three hundred thousand compounds were tested against the SHMT enzyme, producing 24 hits. Among those hits, a subclass was followed with in vivo screening and compounds were promoted to field trials.
265:
The activation of plant responses is often associated with arrested growth and reductions in yield, for reasons that remain unclear. The molecular mechanisms governing plant activators are largely unknown.
89:
Candidate molecules are optimized through a design-synthesis-test-analysis cycle. While compounds eventually are tested on the target organism(s). However, in vitro assays are becoming more common.
23:
has focused on developing molecules that combine low use rates and that are more selective, safer, resistance-breaking and cost-effective. Obstacles include increasing
73:(EPA) over the 1997–2010 period included biological (B), natural product (NP), synthetic (S) and synthetic natural derived (SND) substances. Combining conventional
276:
bacteria by priming immune response without directly activating defense genes. The compounds inhibit two enzymes that inactivate the defense hormone
541:"Novel plant immune-priming compounds identified via high-throughput chemical screening target salicylic acid glucosyltransferases in Arabidopsis"
262:, making them ideal for use in agriculture. Wet-rice farmers across East Asia use plant activators as a sustainable means to enhance crop health.
539:
Noutoshi Y, Okazaki M, Kida T, Nishina Y, Morishita Y, Ogawa T, Suzuki H, Shibata D, Jikumaru Y, Hanada A, Kamiya Y, Shirasu K (September 2012).
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libraries, intermediates from projects in other indications and compound collections from pharmaceutical and animal health companies.
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Lamberth C, Jeanmart S, Luksch T, Plant A (August 2013). "Current challenges and trends in the discovery of agrochemicals".
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81:, NPs accounted for the majority of registrations, with 35.7%, followed by S with 30.7%, B with 27.4% and SND with 6.1%.
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was reported in 2011 and represents a starting point for the design of novel insecticides. This structure led to a
988:
246:
70:
439:"Physical and Molecular Properties of Agrochemicals: An Analysis of Screen Inputs, Hits, Leads, and Products"
242:, IspD enzyme cocrystallized with the inhibitor, a more potent inhibitor with an IC50 of 35 nM was designed.
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238:) of 140 nM in the greenhouse at 3 kg/ha (2.7 lb/acre). Thanks to an x-ray crystal structure of
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The sources of new molecules employ natural products, competitors, universities, chemical vendors,
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31:
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Lindell SD, Pattenden LC, Shannon J (June 2009). "Combinatorial chemistry in the agrosciences".
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Cantrell CL, Dayan FE, Duke SO (June 2012). "Natural products as sources for new pesticides".
185:)–gated chloride channel and a binding mode for the meta-diamides, another insecticide class.
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crystal structures yielded synthetically amenable compounds. Common to all inhibitors is the
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is addressed, and can potentially be of use in both contexts. One example is the
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10.1002/(SICI)1521-3773(20000515)39:10<1724::AID-ANIE1724>3.0.CO;2-5
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Stetter J, Lieb F (2000). "Innovation in Crop
Protection: Trends in Research".
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fungicides. Fragments were linked to the warhead to form a virtual library.
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Klebe G (2000). "Recent developments in structure-based drug design".
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are now in the public domain. For example, the crystal structure of a
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209:"warhead", whose interactions and position are well known from the
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519:"Screening technique uncovers five new plant activator compounds"
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62:, reaching 99%, with concomitant environmental improvements.
645:"Chemical crop protection research. Methods and challenges"
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may operate via the same processes. In several cases, a
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and an increasingly stringent regulatory environment.
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284:or SAGTs), providing enhanced disease resistance.
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69:New active ingredient registrations with the US
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16:Scientific researches on pesticides
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189:Fragment- and target-based design
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247:serine hydroxymethyltransferase
71:Environmental Protection Agency
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437:Clarke ED, Delaney JS (2003).
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93:Parallels with pharmaceuticals
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472:Journal of Molecular Medicine
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50:(5), the piperidinylthiazole
864:Persistent organic pollutant
7:
1007:Index of pesticide articles
834:Agricultural spray adjuvant
599:. Nova Science Publishers.
404:Journal of Natural Products
201:fragment-based design with
129:found in agrochemicals are
19:Early twenty-first century
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1002:Integrated Pest Management
849:Integrated pest management
649:Pure and Applied Chemistry
456:10.2533/000942903777678641
37:
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899:Paradox of the pesticides
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596:Pesticide research trends
381:10.1016/j.bmc.2009.03.027
939:Pesticide Action Network
859:Non-pesticide management
593:Tennefy AB (June 2008).
839:Biological pest control
662:10.1351/pac200274122241
338:10.1126/science.1237227
32:combinatorial chemistry
952:The Pesticide Question
557:10.1105/tpc.112.098343
177:model for a related γ-
142:Structure-based design
137:Structure-based design
854:Maximum residue limit
824:Environmental effects
484:10.1007/s001090000084
219:anthranilate synthase
195:fragment-based design
147:scytalone dehydratase
1012:Pesticide categories
282:glucosyltransferases
240:Arabidopsis thaliana
54:, and the emamectin
25:pesticide resistance
231:antisense knockdown
225:Genome-sequencing,
193:Techniques such as
21:pesticide research
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655:(12): 2241–2246.
643:Müller U (2002).
622:(10): 1724–1744.
606:978-1-60456-200-2
416:10.1021/np300024u
179:aminobutyric acid
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742:Bioherbicide
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56:insecticides
45:sulfonylurea
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984:New Zealand
889:Degradation
884:Formulation
874:Application
789:Rodenticide
769:Insecticide
732:Bactericide
273:Pseudomonas
211:strobilurin
1038:Pesticides
1027:Categories
967:By country
924:Resurgence
919:Resistance
829:Fumigation
779:Nematicide
710:Pesticides
525:2014-02-11
521:. Phys.org
288:References
171:ivermectin
151:rice blast
106:homologous
75:pesticides
60:acaricides
52:fungicides
48:herbicides
904:Poisoning
794:Slimicide
784:Piscicide
762:Defoliant
757:Herbicide
752:Fungicide
727:Acaricide
718:Pesticide
354:206548681
199:in silico
163:glutamate
909:Research
671:96664327
636:10934351
575:22960909
500:21314020
492:10954199
424:22616957
389:19349185
346:23950530
175:homology
117:triazole
113:receptor
914:Residue
737:Biocide
566:3480303
326:Science
165:-gated
38:History
974:Canada
894:Misuse
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601:ISBN
571:PMID
488:PMID
420:PMID
385:PMID
342:PMID
280:(SA
236:IC50
183:GABA
100:and
77:and
58:and
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561:PMC
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