1. Introduction
Herbicides refer to a large number of compounds widely used to kill plants that interfere with the growth of desired crops, thereby improving the productivity of the crop system. One group of herbicides that includes compounds generally designated as dinitroanilines has been shown to interfere with plant cells by interrupting mitosis and the formation of multinucleated cells. Research has shown that these effects are due to interference with microtubules, i.e., a cytoskeleton structure that is ubiquitous in eukaryotic cells and plays a fundamental role in several biological processes, including the determination and maintenance of cell shape, the motility of several cell types that use flagella and cilia for locomotion, the intracellular transport of organelles, and the movement of chromosomes during cell division. Other processes involving microtubules are not as well characterized. Previous research has shown that dinitroanilines interfere with microtubules by binding to sites on the surface of the longitudinal contacts established between the tubulin subunits that contain lysine and arginine residues, which in turn bind to the nitrile group of dinitroaniline [1,2].
Microtubules are made of α-and β-tubulin heterodimers that form long (i.e., several µmeters in length), filamentous, tubular structures when polymerized. The number of tubulin isotypes varies according to the organism species (e.g.,six types of α-tubulin and seven types of β-tubulin are found in human cells). They can be very dynamic structures that undergo constant assembly and disassembly in cells. Tubulin molecules may be post-translationally modified by polyglutamylation, polyglycylation, phosphorylation, acetylation, detyrosination/tyrosination, and removal of the penultimate glutamic acid residue found in α tubulins. In addition, an increased number of proteins can interact with microtubules; these proteins are known as microtubule-associated proteins (MAPs)and include dynein, kinesin, etc., all of which interfere with the stability of the microtubules and their function. Further data on microtubule composition and dynamics can be found in an excellent review by Gardner et al. [3].
2. Dinitroanilines
Dinitroanilines correspond to a family of herbicides that were originally discovered through studies evaluating dyes and chemical synthesis intermediates. The most important member of the group is trifluralin, which is widely used in soybean production. The family is divided into the following two subfamilies: the methylanilines, which includes trifluralin, pendimethalin, benefin, dinitramine, fluchloralin, and profluralin, and the sulfonylanilines, which includes oryzalin and nitralin [1,4,5].Initial studies showed that these compounds inhibit cell division by interfering with the assembly of microtubules, thereby interfering with the formation of the plant cell walls and chromosome movement during the mitotic process, which ultimately leads to the appearance of multinucleated cells [6].
One characteristic feature of several pathogenic protozoa is the presence of a large number of structures in which microtubules are a major component. In the case of the Trypanosomatidae family, which includes such important pathogenic species as
In the following text, I will review the literature focused on the effects of herbicides on each group of pathogenic protozoa.
3. Trypanosomatids
The microtubules that are found in trypanosomatids, especially those that are subpellicular, are considered resistant to several compounds that usually depolymerize microtubules found in eukaryotic cells, including colchicine, vinblastine, and vincristine [11]. However, these organisms show some sensitivity to taxol [12]. Research has shown that trifluralin inhibits cell division in several members of the Trypanosomatidae family, including
Some papers have described attempts to use dinitroanilines in vivo. For instance, promising results were observed when using topical applications of dinitroanilines to treat lesions induced by
4. Apicomplexa
More information on the effect of herbicides is available for this group of eukaryotic microorganisms, especially
N1,N1-dipropyl-2,6-dinitro-4-(trifluoromethyl)-1,3benzenediamine is the most potent agent against
5. Anaerobic protozoa
Oryzalin was tested against
6. Trifluralin associated with phospholipid analogues
Phospholipid analogues, such as miltefosine, have been shown to be very effective against parasitic protozoa, especially
Acknowledgments
The work conducted in the author’s laboratory was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Financiadora de Estudos e Projetos-FINEP, Fundação de Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES, and Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro-FAPERJ.
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