Modern agrochemical research: a missed opportunity for drug discovery?

Delaney, John S.; Clarke, Eric D.; Hughes, David L.; Rice, M. J.

doi:10.1016/j.drudis.2006.07.002

Cited by 61 publications

(52 citation statements)

References 42 publications

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“…Thus a virtual screening method takes as input all those molecules that might be acquired (or synthesised) and tested, and then outputs those few that should be tested. Similar techniques are also used for the discovery of NCEs in the agrochemicals industry [4], but we shall restrict ourselves here to the problems of drug discovery.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of machine-learning methods for ligand-based virtual screening

Chen

Harrison

Papadatos

et al. 2007

J Comput Aided Mol Des

112

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Abstract. Machine-learning methods can be used for virtual screening by analysing the structural characteristics of molecules of known (in)activity, and we here discuss the use of kernel discrimination and naive Bayesian classifier methods for this purpose. We report a kernel method that allows the processing of molecules represented by binary, integer and real-valued descriptors, and show that it is little different in screening performance from a previously described kernel that had been developed specifically for the analysis of binary fingerprint representations of molecular structure. We then evaluate the performance of a naive Bayesian classifier when the training-set contains only a very few active molecules. In such cases, a simpler approach based on group fusion would appear to provide superior screening performance, especially when structurally heterogeneous datasets are to be processed.

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Section: Introductionmentioning

confidence: 99%

Evaluation of machine-learning methods for ligand-based virtual screening

Chen

Harrison

Papadatos

et al. 2007

J Comput Aided Mol Des

112

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“…This is caused by the requirement to agrochemicals to resist to metabolic attack by the pest species. [30,40,41] Nevertheless, it can be stated that the conclusions reached in all these studies were very similar to each other and to the Lipinski's work. Leads are usually smaller and less lipophilic than launched active ingredients; MW and lipophilicity generally increase during the lead-to-drug optimization process.…”

Section: Similarity Of Drugs and Agrochemicalsmentioning

confidence: 55%

“…One of the exceptions is fluconazole, a fungicide product discovered by the pharmaceutical sector that is now used as a pharmaceutical but also was patented as a chemical with applications in crop production. [29][30][31][32][33][34] Bioavailability is highly important for any bioactive agent. The Lipinski's Rule of Five [35] can be considered as the reference for defining physicochemical and structural parameters for oral drug bioavailability.…”

Section: Similarity Of Drugs and Agrochemicalsmentioning

confidence: 99%

Potential of agricultural fungicides for antifungal drug discovery

Jampílek

2015

Expert Opinion on Drug Discovery

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While it is true that only a small fraction of fungal species are responsible for human mycoses, the increasing prevalence of fungal diseases has highlighted an urgent need to develop new antifungal drugs, especially for systemic administration. This contribution focuses on the similarities between agricultural fungicides and drugs. Inorganic, organometallic and organic compounds can be found amongst agricultural fungicides. Furthermore, fungicides are designed and developed in a similar fashion to drugs based on similar rules and guidelines, with fungicides also having to meet similar criteria of lead-likeness and/or drug-likeness. Modern approved specific-target fungicides are well-characterized entities with a proposed structureactivity relationships hypothesis and a defined mode of action. Extensive toxicological evaluation, including mammalian toxicology assays, is performed during the whole discovery and development process. Thus modern agrochemical research (design of modern agrochemicals) comes close to drug design, discovery and development. Therefore, modern specific-target fungicides represent excellent lead-like structures/models for novel drug design and development.

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“…In addition, according to the results reported recently, some quinoline derivatives and their analogues/isosteres also showed noteworthy herbicidal activities [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Although at present approximately 20 mechanisms of action of herbicides are known [21], over 50% of commercially available herbicides act by reversible binding to photosystem II (PS II), a membrane-protein complex in the thylakoid membranes, which catalyses the oxidation of water and the reduction of plastoquinone [22], and thereby inhibit photosynthesis [23][24][25]. Some organic compounds, possessing an amide (-NHCO-) group, e.g., substituted anilides [11,[15][16][17][18]20], or a wide variety of compounds containing the quinoline system [9,10,[12][13][14]19] were found to interact with tyrosine radicals Tyr Z and Tyr D (or their surroundings) which are situated in D 1 and D 2 proteins on the donor side of PS II.…”

Section: Introductionmentioning

confidence: 99%

Preparation and Herbicidal Activity of Halogenated 8-Hydroxyquinoline-2-carboxanilides

Kos

Machalova

Peško

et al. 2013

Proceedings of the 17th International Electronic Conference on Synthetic Organic Chemistry

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Abstract:In this study a series of twelve ring-substituted 8-hydroxyquinoline-2-carboxanilides was prepared and characterized. The discussed compounds were prepared by using microwave-assisted synthesis. The compounds were tested for their activity related to inhibition of photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. The compounds were found to inhibit PET in photosystem II. Significant PET-inhibiting activity was observed for meta-substituted compounds showing IC 50 values close to that of photosystem II herbicide DCMU (3-(3,4-dichlorophenyl)-1,1-dimethylurea, IC 50 = 1.9 μmol/L). N-(3-Fluorophenyl)-8-hydroxyquinoline-2-carboxamide showed the highest PET inhibition. The activity of meta-and para-substituted compounds strongly decreased with lipophilicity increase and electron-withdrawing effect. No influence of any of these parameters on PET-inhibiting activity of ortho-substituted compounds was observed.

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Modern agrochemical research: a missed opportunity for drug discovery?

Cited by 61 publications

References 42 publications

Evaluation of machine-learning methods for ligand-based virtual screening

Evaluation of machine-learning methods for ligand-based virtual screening

Potential of agricultural fungicides for antifungal drug discovery

Preparation and Herbicidal Activity of Halogenated 8-Hydroxyquinoline-2-carboxanilides

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