Topic
Dinitroaniline
About: Dinitroaniline is a research topic. Over the lifetime, 241 publications have been published within this topic receiving 4947 citations. The topic is also known as: dinitroanilines.
Papers published on a yearly basis
1 / 2
Papers
TL;DR: The results demonstrate pharmacological differences between plant and animal tubulins and indicate that the most sensitive mode of action of the dinitroaniline herbicides is the direct poisoning of MT dynamics in cells of higher plants.
Abstract: The effects of oryzalin, a dinitroaniline herbicide, on chromosome behavior and on cellular microtubules (MTs) were examined by light microscopy and immunogold staining, respectively, in endosperm cells from Haemanthus katherinae Bak. Brief treatments with 1.0·10-8 M oryzalin reduced markedly the migration rate of anaphase chromosomes and 1.0·10-7 M oryzalin stopped migration abruptly. Oryzalin (1.0·10-7 M) depolymerized MTs and prevented the polymerization of new MTs at all stages of the mitotic cycle. The chromosome condensation cycle was unaffected by oryzalin. Endothelial cells from the heart of Xenopus leavis showed no chromosomal or microtubular rearrangements after oryzalin treatment. The inhibition by oryzalin of the polymerization of tubulin isolated from cultured cells of Rosa sp. cv. Paul's scarlet was examined in vitro by turbidimetry, electron microscopy and polymer sedimentation analysis. Oryzalin inhibited the rapid phase of taxol-induced polymerization of rose MTs at 24°C with an apparent inhibition constant (K
i
) of 2.59·106 M. Shorter and fewer MTs were formed with increasing oryzalin concentrations, and maximum inhibition of taxol-induced polymerization occurred at approx. 1:1 molar ratios of oryzalin and tubulin. Oryzalin partially depolymerized taxol-stabilized rose MTs. Ligand-binding experiments with [14C]oryzalin demonstrated the formation of a tubulin-oryzalin complex that was time- and pH-dependent. The tubulin-oryzalin interaction (24°C, pH 7.1) had an apparent affinity constant (K
app) of 1.19·105 M-1. Oryzalin did not inhibit taxol-induced polymerization of bovinebrain MTs and no appreciable binding of oryzalin to brain tubulin or other proteins was detected. The results demonstrate pharmacological differences between plant and animal tubulins and indicate that the most sensitive mode of action of the dinitroaniline herbicides is the direct poisoning of MT dynamics in cells of higher plants.
392 citations
TL;DR: All dinitroanilines appear to block nuclear division by inhibition of intranuclear spindle formation, but other cytoskeletal components were differentially affected by the various drugs tested.
158 citations
TL;DR: It is shown that the mutated gene is the cause of the herbicide resistance of goosegrass by using it to transform maize and confer resistance to dinitroaniline herbicides.
Abstract: The dinitroaniline herbicides (such as trifluralin and oryzalin) have been developed for the selective control of weeds in arable crops. However, prolonged use of these chemicals has resulted in the selection of resistant biotypes of goosegrass, a major weed. These herbicides bind to the plant tubulin protein but not to mammalian tubulin1. Here we show that the major α-tubulin gene of the resistant biotype has three base changes within the coding sequence. These base changes swap cytosine and thymine, most likely as the result of the spontaneous deamination of methylated cytosine. One of these base changes causes an amino-acid change in the protein: normal threonine at position 239 is changed to isoleucine. This position is close to the site of interaction between tubulin dimers in the microtubule protofilament. We show that the mutated gene is the cause of the herbicide resistance by using it to transform maize and confer resistance to dinitroaniline herbicides. Our results provide a molecular explanation for the resistance of goosegrass to dinitroanaline herbicides, a phenomenon that has arisen, and been selected for, as a result of repeated exposure to this class of herbicide.
157 citations
TL;DR: It is proposed that the dinitroanilines act through a novel mechanism, by disrupting M-N loop contacts, which represent the first class of drugs that act on α-tubulin function.
Abstract: Protozoan parasites are remarkably sensitive to dinitroanilines such as oryzalin, which disrupt plant but not animal microtubules. To explore the basis of dinitroaniline action, we isolated 49 independent resistant Toxoplasma gondii lines after chemical mutagenesis. All 23 of the lines that we examined harbored single point mutations in α-tubulin. These point mutations were sufficient to confer resistance when transfected into wild-type parasites. Several mutations were in the M or N loops, which coordinate protofilament interactions in the microtubule, but most of the mutations were in the core of α-tubulin. Docking studies predict that oryzalin binds with an average affinity of 23 nM to a site located beneath the N loop of Toxoplasma α-tubulin. This binding site included residues that were mutated in several resistant lines. Moreover, parallel analysis of Bos taurus α-tubulin indicated that oryzalin did not interact with this site and had a significantly decreased, nonspecific affinity for vertebrate α-tubulin. We propose that the dinitroanilines act through a novel mechanism, by disrupting M-N loop contacts. These compounds also represent the first class of drugs that act on α-tubulin function.
156 citations
TL;DR: In vitro, radioactive trifluralin showed specific binding to leishmania tubulin but not to mammalian tubulin, and may serve as useful sources of potential antiparasitic agents.
Abstract: The dinitroaniline herbicide trifluralin (alpha, alpha, alpha-trifluoro-2,6-dinitro-N, N-dipropyl-p-toluidine), at micromolar concentrations, selectively inhibited both proliferation and differentiation of the parasitic protozoan Leishmania mexicana amazonensis. In vitro, radioactive trifluralin showed specific binding to leishmania tubulin but not to mammalian tubulin. Because herbicides such as trifluralin are economical and are considered safe for man and domesticated animals, they may serve as useful sources of potential antiparasitic agents.
126 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 3 |
| 2020 | 4 |
| 2019 | 1 |
| 2018 | 7 |
| 2017 | 3 |
| 2016 | 5 |