New strigolactone mimics: Structure–activity relationship and mode of action as germinating stimulants for parasitic weeds

Strigolactones (SLs) are new plant hormones with varies important bio-functions. This Letter deals with germination of seeds of parasitic weeds. Natural SLs have a too complex structure for synthesis. Therefore, there is an active search for SL analogues and mimics with a simpler structure with retention of activity. SL analogues all contain the D-ring connected with an enone moiety through an enol ether unit. A new mechanism for the hydrolysis SL analogues involving bidentate bound water and an α,β-hydrolase with a Ser-His-Asp catalytic triad has been proposed. Newly discovered SL mimics only have the D-ring with an appropriate leaving group at C-5. A mode of action for SL mimics was proposed for which now supporting evidence is provided. As predicted an extra methyl group at C-4 of the D-ring blocks the germination of seeds of parasitic weeds.     

Strigolactone analogs derived from ketones using a working model for germination stimulants as a blueprint

Strigolactones are important signaling compounds in the plant kingdom. Here we focus on their germination stimulatory effect on seeds of the parasitic weeds Striga and Orobanche spp. and more particularly on the design and synthesis of new active strigolactone analogs derived from simple cyclic ketones. New analogs derived from 1-indanone, 1-tetralone, cyclopentanone, cyclohexanone and a series of substituted cyclohexanones (including carvone and pulegone) are prepared by formylation of the ketones with ethyl formate followed by coupling with a halo butenolide. Both enantiomers of the analog derived from 1-tetralone have been prepared by employing a homochiral synthon for the coupling reaction. For three other strigolactone analogs the antipodes have been obtained by chromatography on a chiral column. All analogs have an appreciable germinating activity towards seeds of Striga hermomonthica and Orobanche crenata and O. cernua. Stereoisomers having the same configuration at the D-ring as in naturally occurring strigol have a higher stimulatory effect than the corresponding antipodes. The analogs obtained from 1-indanone and 1-tetralone have an activity comparable with that of the well known stimulant GR 24. Analogs derived from 2-phenyl-cylohexanone, carvone and pulegone also have a good germinating response. The results show that the working model for designing new bioactive strigolactones is applicable.     

Strigolactones: new plant hormones in action

Main conclusion

The key step in the mode of action of strigolactones is the enzymatic detachment of the D-ring. The thus formed hydroxy butenolide induces conformational changes of the receptor pocket which trigger a cascade of reactions in the signal transduction.

Abstract

Strigolactones (SLs) constitute a new class of plant hormones which are of increasing importance in plant science. For the last 60 years, they have been known as germination stimulants for parasitic plants. Recently, several new bio-properties of SLs have been discovered such as the branching factor for arbuscular mycorrhizal fungi, regulation of plant architecture (inhibition of bud outgrowth and of shoot branching) and the response to abiotic factors, etc. To broaden horizons and encourage new ideas for identifying and synthesising new and structurally simple SLs, this review is focused on molecular aspects of this new class of plant hormones. Special attention has been given to structural features, the mode of action of these phytohormones in various biological actions, the design of SL analogs and their applications.

     

Comparative analysis of the clastogenicity and cytotoxicity of airborne particulate matter generated during the fire at Schweizerhalle on November 1, 1986

Methanol extracts from 4 pairs of airconditioner filters (one fire-exposed and one control) from various locations (A, B, C and D) at various distances from the site of the fire were examined for their capacity to induce structural chromosomal aberrations and/or cytotoxicity in Chinese hamster V79 cells. Extracts from 2 additional sets of 3 filters which were exposed to urban air for 3 consecutive periods of 10 or 11 days some 4 months after the fire were also tested. Chromosomal aberrations were induced by all filter extracts from location B, as well as by an unused (non-exposed) filter, in a dose-dependent manner. Without the addition of metabolizing enzymes, aberrations were induced only at concentrations which caused more than 95% cell killing. This was not taken as an indication for clastogenic activity of the filter extracts, but was assumed to represent the chromosomal expression of metabolic changes in dying cells. Upon the addition of S9, chromosomal aberrations were induced at biologically relevant survival rates. Under metabolizing conditions, the ranking of the potential of the filter extracts from location B to induce chromosomal aberrations and to cause cell killing was identical. The remaining extracts (locations A, C and D) were therefore tested for cytotoxicity only. The toxicity data indicated that, of 3 pairs of filters, the fire-exposed one was not different from the control. Of the fourth pair (location B), the fire-exposed filter was 2.0-2.5 times more cytotoxic and clastogenic than the control. However, extracts of urban air-exposed filters from this location (exposed in March and April 1987) showed a large variation in toxicity and clastogenicity as well. One was clearly more active than the control (but less than the fire-exposed filter), while the other 2 were either somewhat more or less clastogenic than the control filter. In addition, 4 out of 5 filters from this location were more polluted (as indicated by cytotoxicity) than all the filters from the other locations, irrespective of whether they were fire-exposed or not. It is concluded that the results of this V79 cytotoxicity/clastogenicity test did not confirm the hypothesis that the fire at Schweizerhalle produced clastogenic material at quantities detectable under the conditions employed.     

Synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl beta-D-fructopyranosides and some derivatives

The synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl β-d-fructopyranosides, and some derivatives, employing Sharpless-type catalytic asymmetric dihydroxylation procedures is described. Some aspects of the reactions, including stereoselectivities and chemical evidence for the assigned stereochemistry of the main products are reported.     

Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI tagging: early onset and late peak of shortening in lateral wall

Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge of cardiac contraction timing in healthy persons is scarce. In this work, timing of cardiac contraction was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI myocardial tagging and strain analysis. Both the onset time of circumferential shortening (T(onset)) in early systole and the time of peak circumferential shortening (T(peak)) at end systole were determined. The onset of shortening width (time needed for 20-90% of the left ventricle to start shortening) was small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with earliest onset in the lateral wall and latest onset in the septum (P = 0.001). Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an opposite spatial pattern, with peak shortening occurring earlier in the septum than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments, mainly in the lateral and basal segments. Shortening in these segments continued 58 +/- 14 ms after aortic valve closure, during which circumferential shortening increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction in normal subjects may serve as a reference in detecting mechanical asynchrony due to intraventricular conduction defects or ischemia.     

High-Resolution Postcontrast Time-of-Flight MR Angiography of Intracranial Perforators at 7.0 Tesla

Background and Purpose

Different studies already demonstrated the benefits of 7T for precontrast TOF-MRA in the visualization of intracranial small vessels. The aim of this study was to assess the performance of high-resolution 7T TOF-MRA after the administration of a gadolinium-based contrast agent in visualizing intracranial perforating arteries.

Materials and Methods

Ten consecutive patients (7 male; mean age, 50.4 ± 9.9 years) who received TOF-MRA at 7T after contrast administration were retrospectively included in this study. Intracranial perforating arteries, branching from the parent arteries of the circle of Willis, were identified on all TOF-MRA images. Provided a TOF-MRA before contrast administration was present, a direct comparison between pre- and postcontrast TOF-MRA was made.

Results

It was possible to visualize intracranial perforating arteries branching off from the entire circle of Willis, and their proximal branches. The posterior cerebral artery (P1 and proximal segment of P2) appeared to have the largest number of visible perforating branches (mean of 5.1 in each patient, with a range of 2–7). The basilar artery and middle cerebral artery (M1 and proximal segment M2) followed with a mean number of 5.0 and 3.5 visible perforating branches (range of 1–9 and 1–8, respectively). Venous contamination in the postcontrast scans sometimes made it difficult to discern the arterial or venous nature of a vessel.

Conclusion

High-resolution postcontrast TOF-MRA at 7T was able to visualize multiple intracranial perforators branching off from various parts of the circle of Willis and proximal intracranial arteries. Although confirmation in a larger study is needed, the administration of a contrast agent for high-resolution TOF-MRA at 7T seems to enable a better visualization of the distal segment of certain intracranial perforators.     

Strigolactone analogues and mimics derived from phthalimide, saccharine, p-tolylmalondialdehyde, benzoic and salicylic acid as scaffolds

A series of new strigolactone (SL) analogues is derived from simple and cheap starting materials. These SL analogues are designed using a working model. The first analogue is a modified Nijmegen-1, the second contains saccharin as substituent (bio-isosteric replacement of a carbonyl in Nijmegen-1 by a sulfonyl group) and the third one is derived from p-tolylmalondialdehyde. These new SL analogues are appreciably to highly active as germination stimulants of seeds of Striga hermonthica and Orobanche cernua. The SL analogue derived from saccharin is the most active one. A serendipitous and most rewarding finding is that the compound obtained by a direct coupling of saccharin with the chlorobutenolide exhibits a high germination activity especially towards O. cernua seeds. Two other SL mimics are obtained from benzoic and salicylic aid by a direct coupling reaction with chlorobutenolide, both of them are very active germinating agents. These SL mimics represent a new type of germination stimulants. A tentative molecular mechanism for the mode of action of these SL mimics has been proposed.     

DNA lesions,chromosomal aberrations and G2 delay in CHO cells cultured in medium containing bromo- or chloro-deoxyuridine

Experiments have been performed to investigate whether BrdUrd- and CldUrd-substituted DNA contains lesions causing a delay in cell-cycle progression and induction of chromosomal aberrations. The presence of lesions has been determined directly by alkaline sucrose gradient and nucleoid sedimentation analysis and indirectly by screening for induced chromosomal aberrations. The influence of inhibitors of DNA repair (caffeine and 3-aminobenzamide) or DNA synthesis (hydroxyurea) on the frequencies of such aberrations has been estimated. It is found that BrdUrd and CldUrd are cytotoxic when present in DNA. No randomly located DNA breaks could be detected under neutral conditions, but BrdUrd-substituted DNA was found to contain numerous alkali-labile sites. CldUrd at high concentrations causes G₂ delay, similar to the action of known DNA-damaging agents. The extent of delay depends on the pattern of incorporation of the analogue, i.e., incorporation for two cell cycles causes the longest delay, growth for 12 h in CldUrd followed by 12 h in dThd-containing medium causes a lesser delay and the delay is not significant when the cells are incubated in the analogue for only 12 h prior to fixation. Numerous chromatid type aberrations are present in cells incubated at the highest CldUrd concentration, and their induction follows the pattern of induction of G₂ delay, indicating the sharing of a common lesion. Caffeine, 3-aminobenzamide and hydroxyurea increase the number of chromosomal aberrations when added 2 h before fixation. The significance of these results is discussed.