The task of inventing and developing active ingredients with useful biological activities requires a search for novel chemical substructures. This process may trigger the discovery of whole classes of chemicals of potential commercial interest. Similar biological effects can often be achieved by completely different compounds. However, compounds within a given structural family may exhibit quite different biological activities depending on their interactions with different intracellular proteins like enzymes or receptors. By varying the functional groups and structural elements of a lead compound, its interaction with the active site of the target protein, as well as its physicochemical, pharmacokinetic, and dynamic properties can be improved. In this context, the introduction of fluorine into active ingredients has become an important concept in the quest for a modern crop protection product with optimal efficacy, environmental safety, user friendliness, and economic viability. Fluorinated organic compounds represent an important and growing family of commercial agrochemicals. A number of recently developed agrochemical candidates represent novel classes of chemical compounds with new modes of action; several of these compounds contain new fluorinated substituents. However, the complex structure-activity relationships associated with biologically active molecules mean that the introduction of fluorine can lead to either an increase or a decrease in the efficacy of a compound depending on its changed mode of action, physicochemical properties, target interaction, or metabolic susceptibility and transformation. Therefore, it is still difficult to predict the sites in a molecule at which fluorine substitution will result in optimal desired effects.

The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection

When plants recognize potential opponents, invading pathogens, wound signals, or abiotic stress, they often switch to a primed state of enhanced defense. However, defense priming can also be induced by some natural or synthetic chemicals. In the primed state, plants respond to biotic and abiotic stress with faster and stronger activation of defense, and this is often linked to immunity and abiotic stress tolerance. This review covers recent advances in disclosing molecular mechanisms of priming. These include elevated levels of pattern-recognition receptors and dormant signaling enzymes, transcription factor HsfB1 activity, and alterations in chromatin state. They also comprise the identification of aspartyl-tRNA synthetase as a receptor of the priming activator β-aminobutyric acid. The article also illustrates the inheritance of priming, exemplifies the role of recently identified priming activators azelaic and pipecolic acid, elaborates on the similarity to defense priming in mammals, and discusses the ...

Priming for Enhanced Defense

Contamination of vineyard soils with fungicides: a review of environmental and toxicological aspects.

Imidazole ring is an important five-membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable electron-rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. The related research and developments of imidazole-based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous imidazole-based compounds as clinical drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potency, which have shown the enormous development value. This work systematically gives a comprehensive review in current developments of imidazole-based compounds in the whole range of medicinal chemistry as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents, together with their potential applications in diagnostics and pathology. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic imidazole-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.

Comprehensive Review in Current Developments of Imidazole‐Based Medicinal Chemistry

Advances in understanding molecular mechanisms of fungicide resistance and molecular detection of resistant genotypes in phytopathogenic fungi

Strobilurins are one of the most important classes of agricultural fungicide. Their invention was inspired by a group of fungicidally active natural products. The outstanding benefits they deliver are currently being utilised in a wide range of crops throughout the world. First launched in 1996, the strobilurins now include the world's biggest selling fungicide, azoxystrobin. By 2002 there will be six strobilurin active ingredients commercially available for agricultural use. This review describes in detail the properties of these active ingredients--their synthesis, biochemical mode of action, biokinetics, fungicidal activity, yield and quality benefits, resistance risk and human and environmental safety. It also describes the clear technical differences that exist between these active ingredients, particularly in the areas of fungicidal activity and biokinetics.

The strobilurin fungicides.

Resistance to QoI fungicides in Pyrenophora teres (Dreschsler) and P. tritici-repentis (Died.) Dreschsler was detected in 2003 in France and in Sweden and Denmark respectively. Molecular analysis revealed the presence of the F129L mutation in resistant isolates of both pathogens. In 2004, the frequency of the F129L mutation in populations of both pathogens further increased. The G143A mutation was also detected in a few isolates of P. tritici-repentis from Denmark and Germany. In 2005, the F129L mutation in P. teres increased in frequency and geographical distribution in France and the UK but remained below 2% in Germany, Switzerland, Belgium and Ireland. In P. tritici-repentis, both mutations were found in a significant proportion of the isolates from Sweden, Denmark and Germany. The G143A mutation conferred a significantly higher level of resistance (higher EC50 values) to Qo inhibitors (QoIs) than did the F129L mutation. In greenhouse trials, resistant isolates with G143A were not well controlled on plants sprayed with recommended field rates, whereas satisfactory control of isolates with F129L was achieved. For the F129L mutation, three different single nucleotide polymorphisms (SNPs), TTA, TTG and CTC, can code for L (leucine) in P. teres, whereas only the CTC codon was detected in P. tritici-repentis isolates. In two out of 250 isolates of P. tritici-repentis from 2005, a mutation at position 137 (G137R) was detected at very low frequency. This mutation conferred similar resistance levels to F129L. The structure of the cytochrome b gene of P. tritici-repentis is significantly different from that of P. teres: an intron directly after amino acid position 143 was detected in P. teres which is not present in P. tritici-repentis. This gene structure suggests that resistance based on the G143A mutation may not occur in P. teres because it is lethal. No G143A isolates were found in any P. teres populations. Although different mutations may evolve in P. tritici-repentis, the G143A mutation will have the strongest impact on field performance of QoI fungicides.

Cytochrome b gene sequence and structure of Pyrenophora teres and P. tritici-repentis and implications for QoI resistance

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ps.813

Review: The strobilurin fungicides

Dave W. Bartlett, John M. Clough, Chris R. A. Godfrey, Jeremy R. Godwin, Alison A. Hall, Steve P. Heaney and Steve J. Maund from Syngenta at Jealott's Hill International Research Centre discuss the biology, ecology and resistance management of the strobilurins, especially picoxystrobin, the latest member of the class.

Jeremy Robert Godwin

Papers

The strobilurin fungicides.

Cytochrome b gene sequence and structure of Pyrenophora teres and P. tritici-repentis and implications for QoI resistance

Review: The strobilurin fungicides

Understanding the strobilurin fungicides

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: pyridazines.