HerbiPAD: a free web platform to comprehensively analyze constitutive property and herbicide‐likeness to estimate chemical bioavailability

Abstract

BACKGROUND Herbicides, as efficient weed control measures, play a crucial role in ensuring food security. The emergence of herbicide‐resistant weeds has negatively affected food security and promoted the demand for new and improved herbicides. The balance between bioavailability and the potency of a compound is one of the most pressing challenges in the development of novel ideal herbicides. Herbicide‐likeness analysis is crucial for the evaluation of this balance and thus may help to address this issue. Many herbicide‐likeness analysis methods have been developed to screen potential novel lead compounds. However, there remains a lack of user‐friendly and integrated tools to comprehensively evaluate herbicide‐likeness. RESULTS Herbicide‐likeness of compounds was assessed through integrated analysis incorporating the physicochemical properties of commercial herbicides, a qualitative rule, and three quantitative scoring functions developed for evaluating herbicide‐likeness. HerbiPAD (http://agroda.gzu.edu.cn:9999/ccb/database/HerbiPAD/) is a free web platform integrated with the collected database and scoring model. This platform contains 542 approved herbicides and > 29 000 physicochemical descriptors. The accuracy of HerbiPAD in distinguishing known herbicides from nonherbicides was 84.2%. In the case study, HerbiPAD evaluated 60 new compounds from seven different herbicide targets, and the accuracy of predicting better bioavailability was 83.3%. CONCLUSIONS HerbiPAD was designed to quickly and efficiently evaluate herbicide‐likeness by integrating qualitative and quantitative analyses. The simple and effective interpretation of the analysis interface may help noncomputational experts understand herbicide‐likeness. © 2020 Society of Chemical Industry

In Silico Resources of Drug-Likeness as a Mirror: What Are We Lacking in Pesticide-Likeness?

“…Today, the number of approved pesticides is more than twice that reported in 2001. On the basis of the characteristics of small molecules that have been approved for pesticides in the past decade, we collected more than 1300 commercial pesticides and calculated 10 properties, and the latest MW cutoff will now reach 650 Da, 19 as shown in Figure 2. For the parameter-based method, its cutoff value is the distribution of most molecules.…”

“…They developed quantitative estimates of insecticide-likeness (QEI), fungicide-likeness (QEF), herbicide-likeness (QEH), and pesticide-likeness (QEP), with an AUC value of 0.7. In addition, Wang et al, 70 Jia et al, 71 and Huang et al 19 used the Gaussian scoring function, desirability function, and Bayesian probability theory to analyze the fungicide-likeness, insecticide-likeness, and herbicide-likeness of compounds, respectively. Their respective AUC values were 0.769−0.825, 0.739−0.872, and 0.718− 0.842.…”

“…In comparison to FungiPAD, the herbicide physicochemical property analysis database (HerbiPAD) concentrates on comprehensive analysis of herbicide-likeness. 19 HerbiPAD contains 37 PPS and 3 in silico ADMET models, with AUC values between 0.718 and 0.842, covering 542 approved herbicides. In comparison to HerbiPAD, BioTransformer focuses on small molecule metabolism prediction and metabolite identification in human tissues, human gut microbiota, and environmental microorganisms.…”

“…Subsequently, the method of the quantitative estimate of pesticide-likeness (QEP) was developed. In addition, many approaches to pesticide-likeness have been reported, including EC 50 database, BeeTox, and HerbiPAD . The discovery of drug and pesticide candidates has been effectively promoted and accelerated by these computational approaches.…”

Refining physico-chemical rules for herbicides using an antimalarial library

“…Since the advent of Lipinski's rules for oral drugs in 1997 several studies have analysed the physicochemical parameters of herbicides [20][21][22][23]28 . Where the underpinning datasets were made known, these consisted of commercial herbicides, so none of these studies considered initial herbicidal hits that then failed in foliar applications 20,22,23 .…”