Selecting the right compounds for screening: does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals?

Abstract

Large numbers of compounds are now available through combinatorial chemistry and from compound vendors to screen for lead-level agrochemical activity. The likelihood that compounds with whole-organism activity will be discovered can be increased if compounds with physicochemical parameters consistent with transport to the target site are selected for screening. Certain ranges of simple parameters (molecular mass, log P, hydrogen-bond donors and acceptors, rotatable bonds) have been correlated with oral bioavailability of drugs. The distribution of these parameters for commercial insecticides and post-emergence herbicides was examined and ranges consistent with whole-organism activity are proposed for the two classes of agrochemical. The most significant difference identified between drugs and these two classes of agrochemicals was the lower numbers of hydrogen-bond donors allowed in the latter cases. The frequency with which certain functional groups occur in drugs and agrochemicals was also compared.

Potential of agricultural fungicides for antifungal drug discovery

“…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.…”

Application Of Nanotechnology In Agriculture And Food Industry, Its Prospects And Risks

“…This nano-DEPA showed 8-fold lower median lethal concentration (48 h) for C. tritaeniorhynchus 3rd instar larvae (0.052 mg/dm 3 ) than bulk DEPA (0.416 mg/dm 3 ). Chitosan-coated nanoformulations of pyrifluquinazon were found to modify behaviour by rapid feeding cessation, so that insects (eg, green peach aphid, Myzus persicae) starve to death [177].…”

“…The antiparasitic activities of TiO 2 NPs synthesized by utilizing leaf aqueous extract of Catharanthus roseus against the adults of hematophagous fly, Hippobosca maculata Leach and sheep-biting louse, Bovicola ovis Schrank were evaluated by Velayutham et al [202]. The maximum activity of synthesized TiO 2 NPs was observed against H. maculata and B. ovis with LD 50 values of 7.09 and 6.56 mg/dm 3 , respectively, indicating that the use of TiO 2 NPs can be considered as an innovative alternative approach to control the hematophagous fly and sheep-biting louse. Moreover, Marimuthu et al [203] reported excellent anti-lousicidal activity of AgNPs against sheep body louse, B. ovis Schrank and human head louse, Pediculus humanus capitis De Geer.…”

“…Fe 3 O 4 NPs (13 nm) applied to basil plants significantly enhanced total chlorophyll, total carbohydrate, essential oil levels, iron content, plant height, branches/plant, leaves/plant, fresh weight and dry weight, and foliar spray treatment was found to be more effective than soil addition of nanofertilizer [262]. Fe 3 O 4 NPs applied at the concentration of 0.75 g/dm 3 in the form of spray on soybean plants increased leaf and pod dry weight, and application of 0.5 g/dm 3 Fe 3 O 4 NPs resulted in the highest grain yield, showing 48% increase in comparison with the control [263]. Fe 3 O 4 NPs were also found to facilitate the photosynthate and iron transfer to the leaves of peanut [264].…”

“…There are many ways to solubilize certain poorly soluble active ingredients, but these methods are limited by particular structures with certain properties in regard to their chemistry or, for example, to their molecular size or conformation. Generally strategies/structural modifications to improve permeability are based on a few fundamental concepts: reduction of ionizability, increase of lipophilicity, reduction of polarity or reduction of hydrogen bond donors or acceptors [1][2][3][4]. Formulations [77][78][79][80][81][82][83][84][85].…”