Biology subjects

Sukhoverkov, K. V.

Publications and source records attributed to Sukhoverkov, K. V..

4 recordsLinked to original sources

bioRxiv2021

Inhibition of chloroplast translation as a new target for herbicides

The rise in herbicide resistance over recent decades threatens global agriculture and food security and so discovery of new modes of action is increasingly important. Here we reveal linezolid, an oxazolidinone antibiotic that inhibits microbial translation, is also herbicidal. To validate the herbicidal mode of action of linezolid we confirmed its micromolar inhibition is specific to chloroplast translation and did not affect photosynthesis directly. To assess the herbicide potential of linezolid, testing against a range of weed and crop species found it effective pre- and post-emergence. Using structure-activity analysis we identified the critical elements for herbicidal activity, but importantly also show, using antimicrobial susceptibility assays, that separation of antibacterial and herbicidal activities was possible. Overall these results validate chloroplast translation as a viable herbicidal target.

plant biology↗

bioRxiv2021

Herbicidal activity of fluoroquinolone derivatives

Development of herbicides with novel modes of action are crucial for weed control and to hinder herbicide resistance. An attractive novel herbicidal target is plant DNA gyrase, which has been demonstrated to be effectively inhibited by the known antimicrobial ciprofloxacin. Despite this good herbicidal activity ciprofloxacin is not suitable as a herbicide due to its antimicrobial activity, therefore, a diverse library of analogues was analysed to gain insight into the aspects required for herbicidal activity. This analysis revealed significant structural modifications were tolerated and that the fluoride at C-6 and a cyclic amino group at C-7 were not crucial for herbicidal activity. The analysis also revealed that these modifications also affected the antibacterial activity with one compound demonstrating good herbicidal activity and weak antibacterial activity, against both Gram-positive and Gram-negative bacteria.

plant biology↗

bioRxiv2021

A systematic approach for finding herbicide synergies

Combining herbicides into a double dose is a common approach to overcome the potential for herbicide resistance by weeds. Many herbicide mixtures can be antagonistic and they are rarely synergistic. Here, 24 commercial herbicides, each representing a mode of action were used to create a matrix of all 276 unique combinations to search for new synergies in agar with Arabidopsis thaliana. Herbicides were used at an appropriate sub-lethal dose such that any synergies gave visible growth inhibition. We found five synergies including three new ones, namely mesotrione-norflurazon, mesotrione-clethodim and paraquat-clomazone. All three new synergies were reproducible in soil-grown conditions. Interestingly, all three new combinations included a bleaching herbicide, suggesting synergy might be a class specific phenomenon. We also found that mesotrione-norflurazon and mesotrione-clethodim combinations remained synergistic against lettuce (Lactuca sativa), but not tef (Eragrostis tef). Our study shows that screening herbicide mixtures against A. thaliana is an efficient approach for finding rare herbicide synergies.

plant biology↗

bioRxiv2020

Refining physico-chemical rules for herbicides using an antimalarial library

Successful herbicides, like drugs, have physico-chemical properties that usually fall within certain limits. A recent analysis of 334 herbicides showed similar properties to the rule of five for human orally-delivered drugs, but herbicides diverged from this for proton donors, partition coefficients and molecular weight. To refine rules for herbicides, we exploited the close evolutionary relationship between P. falciparum and plants by screening the Malaria Box, a 400-compound library composed of novel chemical scaffolds with activity against blood stage malaria parasite Plasmodium falciparum. A high proportion (52 of 400) were herbicidal to Arabidopsis thaliana on agar plates. Thirty-nine of these 52 herbicidal compounds were tested on soil and 16 compounds were herbicidal. These data were used to predict whether a herbicidal hit found on agar will work on soil-grown plants. The physico-chemical parameters were weighted to logP and formal charge and used to generate weighted scores to a large chemical library of liver-stage effective antimalarial leads. Of the six top-scoring compounds, one had a potency comparable to commercial herbicides. This novel compound MMV1206386 had no close structural matches among commercial herbicides. Physiological profiling suggested that MMV1206386 has a new mode of action and overall demonstrates how weighted rules can help during herbicide discovery programs.

plant biology↗