Rediscovering the bioactivity and ecological role of 1,4-benzoxazinones

Abstract

Compounds of the (2H)-1,4-benzoxazin-3(4H)-one class have attracted the attention of phytochemists since the first isolation of 2,4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA). Extensive research has been carried out on the isolation and synthesis of these materials as well as on the dynamics of their degradation in different systems. This has led to the discovery of a wide variety of compounds that are of high interest from the point of view of phytotoxic, antifungal, antimicrobial, and antifeedant effects among others. The potential application of benzoxazinones and their derivatives as leads for natural herbicide models is a topic of current interest. Furthermore, the importance of degradation on the ecological behaviour of benzoxazinone-producing plants is also being realised, and proposals concerning the role of the degradation products in chemical defence mechanisms have been put forward. There is also increasing interest in the improvement of analytical methodologies, and ecotoxicologic effects, toxicity on target and non-target organisms, and degradation kinetics are also being addressed. The development of new phytotoxicity bioassay techniques represents one of the most important breakthroughs in this respect. Moreover, benzoxazinones and some of their derivatives have been employed in the development of pharmaceuticals. The versatility of the benzoxazinone skeleton, in addition to its relative chemical simplicity and accessibility, makes these chemicals amongst the most promising sources of bioactive compounds that are natural in origin.

Plants Release Precursors of Histone Deacetylase Inhibitors to Suppress Growth of Competitors

“…DIBOA and DIMBOA typically undergo rapid degradation in natural environments. The resulting product APO is a highly potent phytotoxin, which is also the case, although to a lesser extent, for AMPO (Macías et al, 2006(Macías et al, , 2009. The allelochemicals APO and AMPO as well as their precursors have been detected in plants in proximity to DI(M)BOA donor plants (Macías et al, 2014).…”

“…The conservation of the target raises the question how the donor can avoid HDAC inhibition by its own allelochemicals. APO and AMPO are the main stable intermediates that usually develop after precursor substances have been released by plant roots into the rhizosphere; thus, these compounds are not directly produced within the donor plant itself (Belz and Hurle, 2005;Macías et al, 2006Macías et al, , 2009Belz, 2007). Accordingly, neither the APO and AMPO precursors DIBOA and DIMBOA nor the BOA and MBOA intermediates had strong effects on HDAC activity (Supplemental Figure 5).…”

“…In nature, these substances typically undergo rapid degradation via the intermediates benzoxazolin-2(3H)-one (BOA) and 6-methoxybenzoxazolin-2(3H)-one (MBOA). The resulting benzoxazolinone metabolites are much more stable, and in particular, the aminophenoxazinone compounds 2-amino-3H-phenoxazin-3-one (APO) and 2-amino-7-methoxy-3H-phenoxazin-3-one (AMPO) are highly potent phytotoxins (Macías et al, 2006(Macías et al, , 2009. The precursors DIBOA and DIMBOA as well as their degradation products APO and AMPO have been detected in target plants (Macías et al, 2014).…”

Study of the role played by NfsA, NfsB nitroreductase and NemA flavin reductase from Escherichia coli in the conversion of ethyl 2-(2′-nitrophenoxy)acetate to 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIBOA), a benzohydroxamic acid with interesting biological properties

“…Some benzohydroxamic acids isolated from plants such as 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one, known as DIBOA, and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxacin-3(4H)-one, known as DIMBOA (Honkanen and Virtanen 1960;Hamilton et al 1962), exhibit a variety of interesting biological activities as phytotoxic properties, antimicrobial activity as well as antifeedant, antifungal and insecticidal properties (Duke 1986;Macías et al 2006aMacías et al , 2008Macías et al , 2009.…”

Allelochemicals of the phenoxazinone class act at physiologically relevant concentrations

“…2 This particular class of allelochemicals derives from the cyclic hydroxamic acids DIBOA (4-dihydroxy-2H-1,4-benzoxazin-3(4H)-one) and DIMBOA (2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), which are contained in root exudates from many grasses, among them several major crops such as wheat, rice and maize. 3,4 We were able to show that APO and AMPO have the potential to bind to histone deacetylases (HDACs), 2 an evolutionarily highly conserved class of enzymes that govern the accessibility of the DNA by removal of acetyl groups from various amino acid residues of histone proteins. Histone acetylation is a dynamic epigenetic mark that correlates with relaxed chromatin conformation, accessible DNA and transcriptional activity (Fig.…”