Phytochemisrry, Vol 27, No 11, pp 3349-3358, 1988 Pnnted m Great Brltam

0031-9422/88 %300+000 0 1988 Pergamon Press plc

REVIEW ARTICLE NUMBER 39

HYDROXAMIC ACIDS (4-HYDROXY-1,4-BENZOXAZIN-3-ONES), DEFENCE CHEMICALS IN THE GRAMINEAE

HERMANN M NIEMEYER

Facultad de Clenclas, Unlversidad de Chile, Casllla 653, Santiago, Chile

(Recewed 2 June 1988)

Key Word Index-Grammeae, cereals, pest resistance, &ease resistance, Ostr~nu~ nubdah, European corn borer, aphids, hydroxamlc acids, benzoxazmones, DIMBOA

Abstract-Hydroxamlc acids of the type 4-hydroxy-1,4-benzoxazm-3-ones constitute one of the most extensively studied secondary metabohtes m relation to host plant resistance to pests and dtseases They play a maJor role in the defence of cereals against insects, fungi and bacteria, m the detoxlficatlon of herbicides and in allelopathic effects of the crop Although other mechamsms have also a bearing on these effects, more mtensive exploltatlon of hydroxamlc acids in cereal crops 1s mdlcated.

INTRODUCTION

The rising costs of pesticides, the increasing resistance of insects to them and their undesirable effects on the environment, has lead to renewed efforts to describe and to exploit host plant resistance to pests and diseases Cereals, while constituting the mam food crops m the world, have imperfectly described chemical defences Three decades ago, a series of 1,4-benzoxazm-3-ones were discovered m rye plants m relation to resistance of the plants to fungal Infection. The compounds were later found in maize and wheat, and relatlonshlps were estab- lished between their levels in plants and degree of re- sistance of the plant to insects, fungi and bacteria, detoxl- ficatlon of herbicides and allelopathlc effects. These prop- ertles have had a considerable economic Impact in agn- cultural systems.

More than a decade has elapsed since a review on these compounds was published Cl]. Since then, the range of known activities of these compounds has substantially wldened and the understandmg of these actlvlties mcreas- ed It thus seemed worthwhile to attempt to summarize the currently available Information.

Structural diversity

1,4-Benzoxazin-3-ones are naturally present m the plants as 2-/_?-O-D-glucosldes [2, 31, which may be isola- ted If care is taken to inactivate the enzymes m the tissues before extractlon C&6] Aqueous extracts made at room temperature provide the aglucones. Heating of these extracts causes the decomposition of the aglucones to give benzoxazolin-2-ones as main products The reaction is dlscussed m a later section.

The structures of 1,4-benzoxazin-3-ones and related compounds are collected m Fig 1 Some entries deserve additional comments Although DIM,BOA has not been isolated in a pure state, its presence in corn extracts was

inferred from the mass spectrum of a mixture of aglucones [7] and from the mass spectrum of its trimethylsilyl derivative [8] This is consistent with the increase in decomposition rate expected from methoxylatlon of hy- droxamlc acids [9].

The aglucone of HDMBOA-Glc has also eluded efforts to obtain it m pure form, due to its ease of decomposition [lo]. The evidence for the presence of TRIBOA in maize extracts comes only from the mass spectrum of its tris- trlmethylsilyl derivative [S]. Recently, 5-chloro- HMBOA-Glc was isolated as a peracetate from young corn roots, and clalmed to be a natural product. Detaded experimental procedures were unfortunately not reported [ll]. The crystalline structures of DIBOA [12] and HMBOA-Glc [13] have been determmed. In the latter case, the data was used to ascertain that the absolute configuration of the eplmerlc carbon atom was R.

The term hydroxamic acids (Hx), as used m this review, refers to 4-hydroxy-1,4-benzoxazm-3-ones (Fig. 1).

Distrlbutlon

Hydroxamlc acids have been found m members of the followmg genera in the Gramineae: Aegilops [ 141, Arundo [15], Chusquea [15], Coix [13, 161, Elymus [15], hale [17], Sorghum [18; see however refs 19 and 201, Tnpsacum [21], Tritde [22], Trrticum, including an- cient wheats [14] and Zea, including Z. mexlcana (teos- mte) [21]. Hydroxamlc acids have not been found in Avena [19, 201, Hordeum [19, 20,231 or Oriza [20].

There has been a smgle report of benzoxazinones outside the Grammeae: DIBOA-Glc was found in the seeds of Acanthus mollis (Acanthaceae) [24]. Addltional- ly, MBOA was found in the dried roots of Scoparia d&is (Scrophularaceae) [25] However, the treatments suffered by the extracts m this case makes it highly probable that the compound originally in the plant was the correspond- ing hydroxamlc acid.

3349

3350 H M NIEMEYER

OH

H

RZ

O\f

OR3

R’ R’ R’ Abbrewatton References

Hydroxamkc acids ( 4. hydroxy - I,4 - benzoxazm - 3 ones

H H H DIBOA 2 17

H H GIL DIBOA-Clc 17, 37

Me0 H H DIMBOA 35

Me0 H Glc DIMBOA-GIL 35

Me0 Me0 H DlMzBOA 7

Me0 Me0 GIG DIMzBOA-Glc 179

OH H H TRIBOA 8

ktams ( 1,4 . benzoxazm 3 ones )

H H H HBOA

H H GlC HBOA-Gic

Me0 H H HMBOA

Me0 H Glc HMBOA-GIG

Me0 Me0 H HM,BOA

Me0 Me0 ClC HM2BOA-Gk

OH H Glc DHBOA- Glc

3

3

180,181

16,180,182

179

13.183

Methyl derwatlve ( 4 methoxy - I ,4 - benzoxazm 3 one )

OMe Me0 H Glc HDMBOA -Glc 13,184

R* Benzoxazobnones

H H BOA I85

Me0 H MBOA 25,40.81. IX6

Me0 Me0 M*BOA 7

H

Fig 1 1,4-Benzoxaztn-3-ones and benzoxazohn-2-ones from Grammeae

Wlthm the cereals, DIBOA is the mam hydroxamic acid occurrmg in rye, whereas DIMBOA IS the mam one m wheat and maize DJM,BOA has only been found m maize

AnaIysrs of hydroxamrc acrds

Several methods have been utilized to quantltate hy- droxamlc acids m cereal extracts. In a first group of methods, hydroxamlc acids are decomposed to benzoxazo- lmones by heating Quantltatlon of these derivatives IS carried out by chromatographic separation followed by UV spectroscopy [26, 271, spectrofluorimetry [28] or --. mfiared spectrometry LB_/, by isotopic dilution r3ui, by gas chromatography [20,3 11, by high performance liquid chromatography [3% 33], or by visuai rating after thin layer chromatographlc separation [34] The basic as- sumption of these methods is that stolchlometrlc quantl- ties of benzoxazohnones are obtained from decomposr- tlon of hydroxamic acids. This assumption 1s based on the comparison of the final UV spectrum of decomposed

DJMBOA with that of MBOA [35] and the appearance of lsosbestlc points m the UV spectrum of a decomposmg solution of DJBOA [36, but see however ref 373 Both assumptions may not be valid If products with spectral characteristics slmllar to benzoxazolinones or startmg hydroxamlc acids are formed, as has been found to be the case m some Instances [38,39] In fact, it IS clear that the decomposition of DJMBOA to MBOA 1s not quantlta- tlve, the yield of MBOA being a function of pH, tempera- ture, and composltlon of the reaction medmm [40, 411.

Another group of methods 1s based on the quantltatlon of Fe (III) complexes of hydroxamlc acids [19, 42, 431 These methods produce rehable values for total hydrox- amlc a&s wlthrn a series ofrelated- cereals [44_T

Lastly, methods have been developed which allow the quantltatlon of indlvldual hydroxamlc aads, followmg separation by gas chromatography [8. 441, thin layer chromatography [15], or high performance hquld chro- matography C45-471. The latter method [47] utlhzes crude aqueous extracts and its speed. sensltlvlty. reh- ablhty and use of small quantltles of tissue makes It verv

Defence chemicals in the Grammeae 3351

attractive for extensive screening in plant breeding pro- grams.

Hydroxamic acid levels m a plant

Hydroxamic acids, while not present m the seeds of cereals [23, 311, appear upon germmation m maize [48], wheat [23] and rye [23]. Hx levels increase with age reaching a maximum a few days after germination in maize [27,48,49] and m wheat [23] The maximum level attained and the subsequent rate of decrease are depen- dent upon the cultivar studied [48].

Hx are found m all plant parts. The relative levels m aerial parts and in roots varied within species and cultivar analysed [18,48,50,51]. Hx levels are higher in stem than m leaf tissue [S2] Hx were not found m xylem exudates or in guttation drops of maize [53] or wheat [54] plants

Younger leaves contam higher Hx levels than older ones [27, 50, 51, 551. Within a leaf, the distal section contains higher Hx levels than the basal one [47] Hx levels are higher in the vascular bundles than in the complete leaf of maize [53] and wheat [54] plants, and higher m the lateral veins than m the central vein of maize leaves [53]. Hx were not detected m the lower epidermis of wheat leaves [54] In maize seedlings, Hx levels are higher m the stele than m the cortex [53].

Hx levels depend also on extrinsic factors. Iron defi- ciency in the growth medium provokes an increase m Hx levels m maize [56]. Lower growth temperature decreases Hx levels m maize roots [57], but increases Hx levels m aerial parts of wheat seedlings [31] In this latter case, the effect is obscured by the fact that plants grown under low temperature regime were shorter and the sample analysed contained a higher proportion of younger (higher Hx) tissue This effect may also be operating m the finding that a low intensity light regime produced maize plants with higher Hx levels [58], and that rye seedlings grown m the dark showed lower Hx levels than green seedlings [SO]. Longer photophase, between 8 and 16 hr, lead to lower Hx levels [31], without systematic variation m the height of a wheat seedling. In maize, the effect was different: longer photoperiod, although mcreasmg plant fresh weight, did not influence the concentration of either DIMBOA or its glucoside [59].

Finally, while m some maize cultivars the effect of nitrogen application on Hx levels was not significant [56, 601, m others Hx levels increased upon addition of mtrogen [56, 61, 621

Biosynthesis of benzoxazin-3-ones

Benzoxazinones share with tryptophan a substantial part of their biosynthetic pathway. Thus, label from the shikimate precursors qumic acid [63,64] and anthranilic acid [65] were incorporated into the aromatic ring of benzoxazmones The carbon atoms of the heterocychc ring stem from rtbose, C-2 from C-2 of rtbose and C-3 from C-l. The methoxyl group m DIMBOA-related compounds is derived from various Cl sources such as methiomne, glycine and glycerate [64]. An mtermediate of the type l-(ol-carboxy-phenylammo)-l’-deoxyribose-S- phosphate may participate m the biosynthesis of benz- oxazinones [63, 641

The mterconverston of lactams and hydroxamic acids could not be detected m cell-free extracts. However, in experiments with seedlings, label from HBOA was in-

corporated rapidly mto DIBOA, less rapidly into HMBOA and least rapidly mto DIMBOA. These results suggest that the substrates for interconversion are the glucosides, with the lactams being alternatively oxidized at nitrogen or oxidized at the aromatic carbon atom and further methylated [65]. The mittal and final steps m the biosynthesis of benzoxazmones seem to be clear and are shown m Fig. 2.

Inheritance of hydroxamlc actds

The level of hydroxamic acids in maize lme BxBx is conditioned prtmarily by a major, partially dommant gene [66,67]. Monosomic and B-A translocational anal- ysis, coupled with conventional linkage analysis, showed that the benzoxazmless (bx) locus IS m the short arm of chromosome 4, near Rp4 (map position 27) [68]. Inher- itance of DIMBOA was also quantitative m inbred lines of maize [69]. Among these, mbreds B49 and B37 did not possess any gene or genes with dominance effects com- parable to BxBx [67]. Five loci were estimated to condt- tion hydroxamic acid levels in B49, and two loci m B37 C671.

Chemutry of hydroxamlc acrds

Hydroxamic acids decompose to benzoxazohnones with hberation of formic acid. The mechamsm of the reaction appears to mvolve the fast formation of aldol 1, and the rate hmitmg formation of isocyanate 2, as shown m Fig. 3 [36] This mechanism is supported by studies m aprotic solvents, where the aldol has been quantified [70] and the participation of the hydroxamic oxygen atom as a nucleophile has been confirmed [71], and m alcoholic solvents, where the participation of the hydroxamic car- bony1 group in the rate limiting step has been demon- strated [41]. Additionally, higher pH values of the de- composmg media [36, 391 as well as solvents of higher electron donating properties [39] increase the reaction rates and yields of benzoxazohnone, as expected from the mechanism proposed.

Alternative mechanisms have been proposed on the basis of the higher reactivity of the analogues 3 [72] and 4 [lo] methylated at the hydroxamic oxygen, with respect to their correspondmg parent compounds, and the lack of reactivity of compound 5 [72] with an alkylated phenohc hydroxyl group, with respect to DIBOA. These facts may however be rationalized by the proposed mechanism by taking into account the higher nucleophilicity of a meth- oxyl oxygen atom as compared to a hydroxyl oxygen atom, and the possibility of aldol 1 adopting a conform- ation with an intramolecular hydrogen bond between the phenolic hydroxyl and the hydroxamic carbonyl groups, which exposes the aldehyde carbonyl group to attack by the hydroxamic hydroxyl group (structure 6), thus lead- ing to a lower energy transition state.

The reaction of benzoxazmones with nucleophdes re- sembling fragments of biological macromolecules has been studied, m an attempt to provide a chemical ration- ale to their biological activities. In one group of studies, N-acetylated derivatives of benzoxazinones were studied under the assumption that hydroxamic acids would first be derivatized m the recipient organism. Compound 7 underwent nucleophilic substitution to give products of the type 8 and 9 with phenols, indoles and thiols [73], as well as with ammoacid derivatives [74] as models for

3352 H M NIEMEYER

OH OH

J

/

/ HBOA - Clc

/ L

DIBOA- Clc HMBOA-Glc

/ \

DIMBOA-clc HMIBOA-Glc

/

DIM,BOA- GIL

Fig 2 Brosynthcsrs of 1,4-benzoxazin-3-ones

proteins, and with nucieottdes [7q as models for nucfetc acids

It was later shown that dertvattzatton of hydroxamrc acids was not necessary to account for their blologrcal acttvlty [76-781 and m fact, that N-dertvattzatton was netther necessary for their reactton with nucleophrles [9. 797 The reactive sues of DIMBOA were shown to be the nitrogen atom [9] as well as the aldehyde group of the aldol form 1 [79]

fast aNFcHo

6H bH

1

I SIOW

-

2

Frg 3 Mechamsm of decomposttlon ofhydroxdmlc dad5 (Z,4- dlhydroxy-1,4-benzoxazln-3-ones)

Hydroxamrc acids have been assoctated with resistance ofcereals to Insects, fungt and bacteria, wtth triggering the reproductron of grass-feeding mammals, and with allelo- pathtc effects of cereals The presence of hydroxamtc actds has also been related to the detoxtfcatmn of herbtctdes and pesttcrdes, and to the mmeral nutrmon of the plant Addrttonally, they have been shown to be mutagenic agents and to bmd to auxm bmdmg sttes

Re.uscuncr of nm:~ to the Europwn m-n borer, Ostrmta nubtlalrs Much research has been carried out on thts devastating maize pest Inmal reports on plant chemical resistance factors [SO] focused attention on benzoxazol- mones [27, 30, 81-851 It was then suggested that the hydroxamtc acid precursors may be the actual resistance factors [30,86] This hypotheses was later confirmed The correlations between resistance and benzoxazolmone levels were complemented by btoassays m arttfictal diets which showed hydroxamrc acids to be the most active plant components [87]

Maize tissue contamrng dtffercnt Hx levels, when ad- ded to mertdrc diets where borer larvae feed, showed anttbrottc effects, as reflected m larval mortahty, slower development, smaller mdtvtduals, poorer matings, and fewer offspring [SS] Addmonally, diets to which DIMBOA was added showed feeding deterrent effects [X9, SO] This non-preference component to borer re- sistance was also present m field [91] and laboratory [9 1,921 tests.

In a study with a set of mar/e inbred vartettes. correla- tions were found between hydroxamtc acid levels and leaf feeding resistance by first generation (brood) larvae,

Defence chemtcals m the Gramineae 3353

5 6

7 R = H,MeO

Cl

I -N-OH

II _

Slmazme RI = R2 = it

Atrazme R’ = Et. R2 = I-PI

I ON- OH

Hz0 /4 - N’ N

II

DIMBOA

-

Dtazmon

which fed on young maize plants. As the plants aged and found between these variables both in the mbreds and m the hydroxamic acid levels decreased, resistance levels the single crosses [69]. It was suggested that breeding for decreased, except m vartetres m which the Hx levels first brood resistant maize be carried out by selectmg for remained high [48] Resistance levels to leaf feeding high hydroxamtc actd levels m the plant [69, 89,94-981. decreased under greenhouse conditions, with respect to This leads in fact to inbred hnes highly reststant to leaf field condittons [93]. When a diallel set of 11 maize feedmg by first brood borers [99]. Addtttonally, recurrent mbreds was examined for Hx levels and reststance level to selection breeding leads to improved first brood re- first brood larvae, highly significant correlatrons were sistance and DIMBOA levels, each method of selection

3354 H M NIEMEYER

accumulating about the same level of resistance [ lOO] In studies usmg a wider range of maize lures, resistance

both to first and second brood borers could not be solely attributed to hydroxamic acid levels [43, 92, 101, 1021 Sihca content was found to make a sigmficant contribu- tion to resistance to second brood borers [103]. Re- sistance of maize to a related borer, Sesamzu nonagrzozdes, was also attributed to hydroxamtc acids [104]

Reststance to aphids Aphids are among the most important pests of cereals on account of direct feeding damage and transmission of viral diseases Inverse rela- tionships were obtained between Hx levels m a maize plant and mfestation numbers of the corn leaf aphid Rhopalostphum mazdts [105], under both field and green- house conditions [106] Similar relationships were ob- tamed for Hx levels m a wheat plant and mfestation numbers of the rose-gram aphid Metopolophtum dtrhodum [23], the greenbug Schtzaphzs grammum [Sl] and the English gram aphid Sttobton arenae [ 1071 under greenhouse conditions

When severed barley leaves lacking Hx were immersed m DJMBOA containing solutions, the levels of DJM- BOA mcorporated also correlated with mfestation num- bers of M dzrhodum [23] Aphid mfestation numbers were lower m those tissues with lower Hx levels resultmg from older plant [23] or older plant parts [Sl] being studied

DJMBOA exhibited both antibiotic [15,22,23.51, 105, 10881 IO] and antifeedant [109, 1101 effects on cereal aphids when mcorporated into hohdic diets The aphid most sensitive to DJMBOA levels was S. grammum, the least sensitive R matdrs [111] The glucoside of DJMBOA was less active than DJMBOA itself against S graminum [l lo]

Inverse relationships were obtained between DIM- BOA levels m wheat plants and DIMBOA levels m aphids feeding on them [ 1121. This result, coupled with a tendency towards decreased honeydew production and weight gain, mdicated feeding deterrency by DJMBOA also under natural conditions [112]

Reststance tofungt. Infection ratings of a series of maize mbreds to Northern corn leaf blight-producmg fungus Helmmthosporzum turctcum, mverstly correlated with Hx levels m the plants [27,49, 52, 113, 1141. The presence of the Bx allele conferred additional resistance with respect to lines contammg the Hx-deficiency allele bx, both m monogemc resistant Ht and susceptible ht maize lines

Cl151 Germmatton ot spores of H turctcum was mhibtted m

DIMBOA solutions J-1153. Additionally, dtffusates from young maize tissue were more mhtbitory to spore germm- ation and to germ tube lengthenmg than diffusates from older tissue [116]

Linear relationships were described between resistance levels to H turctcum and to leaf feeding by the European corn borer, using a limited number of maize lures m the field [SS] It was suggested that breeding for high Hx levels may increase resistance to European corn borer, Northern corn leaf blight and maize stalk rot (see below)

c991 When a broader array of maize genotypes was

screened, a correlatton between resistance ratings to borer leaf feeding and to H turcicum was not apparent [ 1171 Additionally, recurrent selection for resistance to leaf feeding by the European corn borer affected negative- ly resistance to H turcicum and had no effect on Dtplodta

maydrs stalk rot ratings [118] This pomts again to the complex and diverse nature of resistance phenomena (see section on resistance to the borer).

Histological observations of the mfection of multigemc Cl193 and monogemc Cl201 resistant and susceptible maize lines by H turctcum showed that differences m mycehal growth between resistant and susceptible hnes occurred when the mycehum reached the vascular bun- dles This is consistent with higher levels of hydroxamic acids being found m the vascular bundles [53, 541.

Correlations have also been reported between Hx levels m the plant and resistance of maize to stalk rot D maydzs [ 121, 1221, of wheat to stem rust Pucctnza qramtms [123-1251, of maize to stalk rot caused by kusarnan momhforme [ 1261, Gthberella zeae [ 1261 and Cephalov portum maydzs [98], of rye to snow mold Fusartum nmale [ 127, 1281, of maize to stem and ear mfections caused by Fusarcum yrumrnearum [ 1291

Weed competition resulted m higher DIMBOA con- tent of maize plants. presumably through lower water availabihty, and a concomitant decrease m mfestation by common smut Ustrhzgo maydzs [130] Application of simazme (see section on detoxification of herbicides) increased the levels of DIMBOA and of its glucoside m wheat plants and concomtttantly reduced attack by Erys- tphe gramuus and Cercosporella herpotrrchotdes [59]

In the case of the obligate parasite P grumnus, It was noted that mfection provoked a breakdown of the gluco- side of DIMBOA. The phytotoxic properties of DIM- BOA [76] were suggested to cause the death of the host cells and hence that of the parasites Conversely no correlations were observed between Hx levels m wheat and resistance to various strains of the root rot agent Helmznthosportun satmum [I313 Additionally, although Hx levels m wheat seedhngs were capable of totally mhibitmg Septorza nodorum. m the adult plants they were suggested to be ummportant m the resistance to the fungus [132]. Fmally, the correlation between Hx levels and resistance to P ,grumznts was criticized on the basis that the correlation coefficient substantially decreased when cultivars of extreme resistance ratings were with- drawn [125, 1331

Reststance to hacterra. The mabihty ofcertam species of soft rotting bacteria Erwmm spp to attack matze was attributed to the presence of DIMBOA m the plant [ 1341 Thus, DJMBOA accounted for most of the capacity of maize extracts to inhibit soft rot bacteria non-pathogemc to maize It did so by prolongmg the lag phase of bacterial growth, while the log phase was not altered [134] It was noted however, that after DJMBOA had decomposed m the bacterial medium to non-mhibitory levels, mhibition persisted [135]. The effect could be due to products from the decomposition of DJMBOA. other than MBOA, m the bacterial medium

When the range of strains studied was broadened, it was found that strains pathogemc to maize were more resistant to Hx levels than strains pathogenic to other hosts [136] However, it was also found that several DIMBOA-susceptible strains pathogenic to other hosts produced stalk rot symptoms in DJMBOA- contauung maize plants. It was suggested that DJMBOA was not the primary means of resistance of maize to Erwinia spp

Allelopathic efjkts. Both germmatton and seedlmg growth of velvetleaf Abutdon theophrastr were affected by DIBOA-Glc, DIBOA and BOA, the most active com-

Defence chemicals in the Grammeae 3355

pound being DIBOA [24]. DIBOA and BOA were found to be involved in the well descrtbed allelopathic effects of rye [137, 1381 Compounds were tested m germination and root and stem elongation of monocots and dicots. DIBOA was the most active compound against mono- cots [138, 1393 while BOA was most active against dicots [138].

The symptoms of DIBOA injury on cress Leprdrum satrvum resembled that of the photosynthetic inhibitor herbicides [138]. This result agrees with the known mhtbitory effects of hydroxamic acids on energy meta- bohsm of chloroplasts [76, 771. Similar symptoms by BOA may be related to the presence of a -N-C=0 group [ 1401. Hydroxamic acids may also be responstble for the allelopathtc effects of wheat [141].

Trzggerzng of reproductzon of the montane vole. The onset of reproducttve activity of the montane vole Micro- tus montanus is correlated with beginning of vegetative growth of the grasses and sedges that constitute their mam food source [142]. Plant extracts containing the DIMBOA derived compound MBOA stimulated repro- ductive activity of M montanus [143, 1443. Sttmulatory effects by MBOA on the breedmg performance of M montanus [143-145-J and on reproducttve responses of rats [146] and other vertebrates [143, 1471 were demon- strated

Hx levels m perennial wild Gramineae increased at the onset of the vegetative growth season [ 151, in agreement with the finding of higher Hx levels in younger tissue. Hence, Hx levels may be the naturally occurring envtron- mental cue triggering the reproductive efforts of M. montanus The occurrence of the compounds m the prmctpal food source of the vole, saltgrass Distichlzs strzcta, was demonstrated [147].

Mzneral nutrztion. The mvolvement of Hx in mineral nutrition has been considered on account of their gen- erally high complexation constants The formation con- stants of complexes of DIMBOA and DIMBOA-Glc with ferric ion [ 1481, and those of DIMBOA with several btvalent cations [149, 1501 have been measured. The constants, while several orders of magnitude smaller than those of hydroxamic acids which function m mtcrobtal iron metabolism, are higher than those of other anions mvolved in mineral nutrition, such as citric and malic acids. Calculations based on concentrations of chelating agents m the whole plant indtcated that a substantial proportion of metal ions would be bound to Hx [148, 1491. Knowledge of concentrations of Hx at relevant plant compartments is necessary before a role in mineral nutrition is adscribed to them.

Modzjicatzon of auxin-receptor Interaction. Maize col-

eoptiles contam substances capable of inhibiting the bmdmg of 1-naphthylacettc acid (NAA) to auxm re- ceptors [lSl]. The compounds were initially identified as MBOA and BOA [152]. It was later shown that the parent hydroxamtc acid DIBOA was more active than the corresponding decomposition product BOA [ 153, 1543 The compounds inhibited not only saturable bmd- ing of NAA to auxm receptors, but also auxin-induced coleptile growth [ 1531, providing evidence that the bind- ing sites represent physiological receptor sites for auxin action. Additionally, BOA inhibited radicle elongation of several plant species [ 1551.

The binding affinity of the auxm analogue 2,4-dichlor- ophenoxyacetic acid (2,4-D) was increased by Hx-con- taming extracts [156], a result that has been associated

with greater capacity for detoxtficatton of 2,4-D of plants wtth higher Hx levels [157].

Detoxijkatzon of herbzczdes and pesticides The 2-chloro- s-triazine derrved herbicides atrazme and simazme are of paramount importance in maize production due to the tolerance exhibited by this crop. Detoxification of these herbicides occur by hydroxylation [158], dealkyl- ation [159-1611 or glutathione conjugation [162] The mechanism prevailing in matze is hydroxylation [20, 163-1651. This reaction has been associated with the presence of Hx m the plant. Thus, the Hx-rtch Bx lme of maize is tolerant while the Hx-lackmg bx line zs suscep- tible [66], cereals with lower Hx levels are more suscep- tible than those with higher levels [158, 166, 1671 or less able to detoxify the herbicrdes by hydroxylation [19]; higher Hx levels in a plant attained through added fertilizer are associated with higher hydroxylation capac- ity [61]; lower Hx levels attrtbuted to cold growing condittons increased susceptibility to the herbicides [57], and higher Hx levels were associated with lower actzvity of the herbicides as plant hormones [168]. Fmally, a relationship was described between resistance to stalk rot and corn borer, and tolerance to atrazine and simazme m maize plants [ 1691.

Hydroxylation of these herbicides is catalysed by hy- droxamtc acids [170-1721. It was suggested that a mo- lecular aggregate of DIMBOA was the reactive species [172]. It was later shown, with the use of stable anal- ogues, that the reaction occurred by direct nucleophthc attack of the hydroxamic oxygen atom on the carbonyl bearing the chlorine atom m the herbicide with formation of an mtermediate, from which the hydroxamic acid moiety was later displaced by water [ 1731, confirming an earlier mechanistic hypothesis [158]. In agreement with this mechanism, only s-triazine derrvatives containing a good leaving group are selective for weed control in maize [174]. A similar mechanism may prevail in the detoxifi- cation of the organophosphorous msecticide dtazinon, by hydroxylation catalysed by DIMBOA [175, 176-J.

Mutageniczty. Both DIBOA and DIMBOA were shown to be mutagemc in a test with Salmonella typhzmur- zum TA 100 and TA 98 [ 177,178]. Studies with analogues of these compounds showed that the 2-hydroxyl and 7- methoxyl groups greatly mcreased mutagenic activity These groups are known to enhance the electrophtlic reacttvtty of the parent molecules [9,70,73,79] Mutage- nicity was also assoctated with the ability of the 4-acetoxy compounds to react with DNA and with model nu- cleottdes [75]. It is worthwhile reiterating that hydrox- amic acids have not been found in the grams of cereals

Concluszons

Host plant resistance to pests and diseases is a complex phenomenon in which multiple factors are involved. Factors which may be of major importance in relation to one pest or disease, may only be secondary or not relevant m relation to another. Hydroxamic acids, while of paramount importance m numerous cases of pest and disease resistance of cereals, have been shown to be of lesser importance m others, in which there is a breakdown in the resistance-Hx level correlations, the Inheritance of resistance and of Hx are different, or recurrent selection for resistance to one pest does not lead to the desired effects in the resistance to another pest The present knowledge of the biological activity of hydroxamtc actds

3356 H M NIEMEYER

sllggests that then. further exploltatlon as a s0llrc.e of resistance IS desirable However, the search for addItIona sources of remtame should be contmued

Acknowledyements--I wish to thank the InternatIonal Program

m the Chenucal Sciences (IPICS) at Uppsala Umverslty for

csmtmued support, and m partlculaz for a fellowslup permlttmg

the wrmng of tis. work The kmd hosprtahty of Prnf Jan

Pettersson at Swechsh Umverslty of Agrxxltural Sciences (SLIJ) K gratefully acktw.vledged So IS the help ohtamed from the

hbrary staff at SLU

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