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Strigolactones (SLs) are a class of sesquiterpenoid plant hormones that play a role in the response of plants to various biotic and abiotic stresses. When released into the rhizosphere, they are perceived by both beneficial symbiotic mycorrhizal fungi and parasitic plants. Due to their multiple roles, SLs are potentially interesting agricultural targets. Indeed, the use of SLs as agrochemicals can favor sustainable agriculture via multiple mechanisms, including shaping root architecture, promoting ideal branching, stimulating nutrient assimilation, controlling parasitic weeds, mitigating drought and enhancing mycorrhization. Moreover, over the last few years, a number of studies have shed light onto the effects exerted by SLs on human cells and on their possible applications in medicine. For example, SLs have been demonstrated to play a key role in the control of pathways related to apoptosis and inflammation. The elucidation of the molecular mechanisms behind their action has inspired further investigations into their effects on human cells and their possible uses as anti-cancer and antimicrobial agents.

Strigolactones (SLs) are plant hormones with various functions in development, responses to stress, and interactions with (micro)organisms in the rhizosphere, including with seeds of parasitic plants. Their perception for hormonal functions requires an α,β-hydrolase belonging to the D14 clade in higher plants; perception of host-produced SLs by parasitic seeds relies on similar but phylogenetically distinct proteins (D14-like). D14 and D14-like proteins are peculiar receptors, because they cleave SLs before undergoing a conformational change that elicits downstream events. Structure-activity relationship data show that the butenolide D-ring is crucial for bioactivity. We applied a bioisosteric approach to the structure of SLs by synthetizing analogues and mimics of natural SLs in which the D-ring was changed from a butenolide to a lactam and then evaluating their bioactivity. This was done by using a novel bioassay based on Arabidopsis transgenic lines expressing AtD14 fused to firefly luciferase, in parallel with the quantification of germination-inducing activity on parasitic seeds. The results obtained showed that the in planta bioassay is robust and quantitative, and thus can be confidently added to the SL-survey toolbox. The results also showed that modification of the butenolide ring into a lactam one significantly hampers the biological activity exhibited by SLs possessing a canonical lactonic D-ring.

Strigolactones, a group of terpenoid lactones, control many aspects of plant growth and development, but the active forms of these plant hormones and their mode of action at the molecular level are still unknown. The strigolactone protein receptor is unusual because it has been shown to cleave the hormone and supposedly forms a covalent bond with the cleaved hormone fragment. This interaction is suggested to induce a conformational change in the receptor that primes it for subsequent interaction with partners in the signalling pathway. Substantial efforts have been invested into describing the interaction of synthetic strigolactone analogues with the receptor, resulting in a number of crystal structures. This investigation combines a re-evaluation of models in the Protein Data Bank with a search for new conditions that may permit the capture of a receptor-ligand complex. While weak difference density is frequently observed in the binding cavity, possibly due to a low-occupancy compound, the models often contain features not supported by the X-ray data. Thus, at this stage, we do not believe that any detailed deductions about the nature, conformation, or binding mode of the ligand can be made with any confidence.

In this paper, we synthesized and evaluated the biological activity of structural analogues of natural strigolactones in which the butenolide D-ring has been replaced with a γ-lactam. The key step to obtain the α,β-unsaturated-γ-lactam was an RCM on suitably substituted amides. Strigolactones (SLs) are plant hormones with various developmental functions. As soil signaling chemicals, they are required for establishing beneficial mycorrhizal plant/fungus symbiosis. Beside these auxinic roles, recently SLs have been successfully investigated as antitumoral agents. Peculiar to the SL perception system is the enzymatic activity of the hormone receptor. SARs data have shown that the presence of the butenolide D-ring is crucial to retain the biological activity. The substitution of the butenolide with a lactam might shed light on the mechanism of perception. In the following, a dedicated in silico study suggested the binding modes of the synthesized compounds to the receptor of SLs in plants.

Strigolactones are a class of natural and synthetic compounds that in the past decade have been exciting the scientific community not only for their intriguing biological properties but also for their potential applications in agriculture. These applications range from their use as hormones to modify and/or manage plant architecture, to their use as stimulants to induce seed germination of parasitic weeds and thus control their infestation by a reduced seed bank, to their use as 'biostimulants' of plant root colonisation by arbuscular mycorrhizal fungi, improving plant nutritional capabilities, to other still unknown effects on microbial soil communities. More recently, these compounds have also been attracting the interest of agrochemical companies. In spite of their biological attractiveness, practical applications are still greatly hampered by the low product yields obtainable by plant root exudates, by the costs of their synthesis, by the lack of knowledge of their off-target effects and by the not yet specified or properly identified legislation that could regulate the use of these compounds, depending on the agricultural purposes. The aim of this article is to discuss, in the light of current knowledge, the different scenarios that might play out in the near future with regard to the practical application of strigolactones. © 2016 Society of Chemical Industry., (© 2016 Society of Chemical Industry.)

Modern biology overlaps with chemistry in explaining the structure and function of all cellular processes at the molecular level. Plant hormone research is perfectly located at the interface between these two disciplines, taking advantage of synthetic and computational chemistry as a tool to decipher the complex biological mechanisms regulating the action of plant hormones. These small signaling molecules regulate a wide range of developmental processes, adapting plant growth to ever changing environmental conditions. The synthesis of small bioactive molecules mimicking the activity of endogenous hormones allows us to unveil many molecular features of their functioning, giving rise to a new field, plant chemical biology. In this framework, fluorescence labeling of plant hormones is emerging as a successful strategy to track the fate of these challenging molecules inside living organisms. Thanks to the increasing availability of new fluorescent probes as well as advanced and innovative imaging technologies, we are now in a position to investigate many of the dynamic mechanisms through which plant hormones exert their action. Such a deep and detailed comprehension is mandatory for the development of new green technologies for practical applications. In this review, we summarize the results obtained so far concerning the fluorescent labeling of plant hormones, highlighting the basic steps leading to the design and synthesis of these compelling molecular tools and their applications., (Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.)

Main Conclusion: MAX2/strigolactone signaling in the endodermis and/or quiescent center of the root is partially sufficient to exert changes in F-actin density and cellular trafficking in the root epidermis, and alter gene expression during plant response to low Pi conditions. Strigolactones (SLs) are a new group of plant hormones that regulate different developmental processes in the plant via MAX2, an F-box protein that interacts with their receptor. SLs and MAX2 are necessary for the marked increase in root-hair (RH) density in seedlings under conditions of phosphate (Pi) deprivation. This marked elevation was associated with an active reduction in actin-filament density and endosomal movement in root epidermal cells. Also, expression of MAX2 under the SCARECROW (SCR) promoter was sufficient to confer SL sensitivity in roots, suggesting that SL signaling pathways act through a root-specific, yet non-cell-autonomous regulatory mode of action. Here we show evidence for a non-cell autonomous signaling of SL/MAX2, originating from the root endodermis, and necessary for seedling response to conditions of Pi deprivation. SCR-derived expression of MAX2 in max2-1 mutant background promoted the root low Pi response, whereas supplementation of the synthetic SL GR24 to these SCR:MAX2 expressing lines further enhanced this response. Moreover, the SCR:MAX2 expression led to changes in actin density and endosome movement in epidermal cells and in TIR1 and PHO2 gene expression. These results demonstrate that MAX2 signaling in the endodermis and/or quiescent center is partially sufficient to exert changes in F-actin density and cellular trafficking in the epidermis, and alter gene expression under low Pi conditions.

Strigolactones are a novel class of plant hormones produced in roots that regulate shoot and root development. We previously reported that strigolactone analogs (SLs) induce G2/M cell cycle arrest and apoptosis in a variety of human cancer cells and inhibit tumor growth of human breast cancer xenografts in mice. SLs had no significant influences on non-transformed cells. Here we report for the first time that SLs induce DNA damage in the form of DNA double-strand breaks (DSBs) and activate the DNA damage response signaling by inducing phosphorylation of ATM, ATR and DNA-PKcs and co-localization of the DNA damage signaling protein, 53BP1, with γH2AX nuclear foci. We further report that in addition to DSBs induction, SLs simultaneously impair DSBs repair, mostly homology-directed repair (HDR) and to a lesser extent non-homologous end joining (NHEJ). In response to SLs, RAD51, the homologous DSB repair protein, is ubiquitinated and targeted for proteasomal degradation and it fails to co-localize with γH2AX foci. Interestingly, SLs synergize with DNA damaging agents-based therapeutics. The combination of PARP inhibitors and SLs showed an especially potent synergy, but only in BRCA1-proficient cells. No synergy was observed between SLs and PARP inhibitors in BRCA1-deficient cells, supporting a role for SLs in HDR impairment. Together, our data suggest that SLs increase genome instability and cell death by a unique mechanism of inducing DNA damage and inhibiting DNA repair.

Strigolactones (SLs) are new plant hormones with various developmental functions. They are also soil signaling chemicals that are required for establishing beneficial mycorrhizal plant/fungus symbiosis. In addition, SLs play an essential role in inducing seed germination in root-parasitic weeds, which are one of the seven most serious biological threats to food security. There are around 20 natural SLs that are produced by plants in very low quantities. Therefore, most of the knowledge on SL signal transduction and associated molecular events is based on the application of synthetic analogues. Stereochemistry plays a crucial role in the structure-activity relationship of SLs, as compounds with an unnatural D-ring configuration may induce biological effects that are unrelated to SLs. We have synthesized a series of strigolactone analogues, whose absolute configuration has been elucidated and related with their biological activity, thus confirming the high specificity of the response. Analogues bearing the R-configured butenolide moiety showed enhanced biological activity, which highlights the importance of this stereochemical motif.

Strigolactones (SLs) are plant hormones that regulate the plant response to phosphate (Pi) growth conditions. At least part of SL-signalling execution in roots involves MAX2-dependent effects on PIN2 polar localization in the plasma membrane (PM) and actin bundling and dynamics. We examined PIN2 expression, PIN2 PM localization, endosome trafficking, and actin bundling under low-Pi conditions: a MAX2-dependent reduction in PIN2 trafficking and polarization in the PM, reduced endosome trafficking, and increased actin-filament bundling were detected in root cells. The intracellular protein trafficking that is related to PIN proteins but unassociated with AUX1 PM localization was selectively inhibited. Exogenous supplementation of the synthetic SL GR24 to a SL-deficient mutant (max4) led to depletion of PIN2 from the PM under low-Pi conditions. Accordingly, roots of mutants in MAX2, MAX4, PIN2, TIR3, and ACTIN2 showed a reduced low-Pi response compared with the wild type, which could be restored by auxin (for all mutants) or GR24 (for all mutants except max2-1). Changes in PIN2 polarity, actin bundling, and vesicle trafficking may be involved in the response to low Pi in roots, dependent on SL/MAX2 signalling., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Strigolactones (SLs) are a novel class of plant hormones. Previously, we found that analogs of SLs induce growth arrest and apoptosis in breast cancer cell lines. These compounds also inhibited the growth of breast cancer stem cell enriched-mammospheres with increased potency. Furthermore, strigolactone analogs inhibited growth and survival of colon, lung, prostate, melanoma, osteosarcoma and leukemia cancer cell lines. To further examine the anti-cancer activity of SLs in vivo, we have examined their effects on growth and viability of MDA-MB-231 tumor xenografts model either alone or in combination with paclitaxel. We show that strigolactone act as new anti-cancer agents in inhibition of breast cancer in xenograft model. In addition we show that SLs affect the integrity of the microtubule network and therefore may inhibit the migratory phenotype of the highly invasive breast cancer cell lines that were examined.

Strigolactones (SLs) are a new class of plant hormones whose role has been recently defined in shoot branching, root development and architecture, and nodulation. They are also active in the rhizosphere as signalling molecules in the communication between plants, AMF (arbuscular mycorrhizal fungi) and parasitic weeds. In spite of the crucial and multifaceted biological role of SLs, the current knowledge on the SL biosynthetic pathway and the perception/transduction mechanism is still incomplete. Both genetic and molecular approaches are required to understand the molecular mechanism by which SLs regulate plant development. Our contribution to this topic is the design and synthesis of fluorescent labelled SL analogues to be used as probes for the detection in vivo of the receptor(s). Knowledge of the putative receptor structure will boost the research on analogues of the natural substrates as required for agricultural applications.

Strigolactones are a novel class of plant hormones produced in roots and regulate shoot and root development. We have previously shown that synthetic strigolactone analogues potently inhibit growth of breast cancer cells and breast cancer stem cells. Here we show that strigolactone analogues inhibit the growth and survival of an array of cancer-derived cell lines representing solid and non-solid cancer cells including: prostate, colon, lung, melanoma, osteosarcoma and leukemic cell lines, while normal cells were minimally affected. Treatment of cancer cells with strigolactone analogues was hallmarked by activation of the stress-related MAPKs: p38 and JNK and induction of stress-related genes; cell cycle arrest and apoptosis evident by increased percentages of cells in the sub-G1 fraction and Annexin V staining. In addition, we tested the response of patient-matched conditionally reprogrammed primary prostate normal and cancer cells. The tumor cells exhibited significantly higher sensitivity to the two most potent SL analogues with increased apoptosis confirmed by PARP1 cleavage compared to their normal counterpart cells. Thus, Strigolactone analogues are promising candidates for anticancer therapy by their ability to specifically induce cell cycle arrest, cellular stress and apoptosis in tumor cells with minimal effects on growth and survival of normal cells.

Background: Strigolactones (SLs) are recently identified plant hormones modulating root and shoot branching. Besides their endogenous role within the producing organism, SLs are also key molecules in the communication of plants with arbuscular mycorrhizal (AM) fungi and parasitic weeds. In fact SLs are exuded into the rhizosphere where they act as a host-derived signal, stimulating the germination of the seeds of parasitic plants which would not survive in the absence of a host root to colonize. Similarly, their perception by AM fungi causes extensive hyphal branching; this is a prerequisite for effective root colonization, since it increases the number of potential contact points with the host surface. In spite of the crucial and multifaceted biological role of SLs, there is no information on the receptor(s) which bind(s) such active molecules, neither in the producing plants, or in parasitic weeds or AM fungi., Results: In this work, we applied homology modelling techniques to investigate the structure of the protein encoded by the gene Dwarf14, which was first identified in rice as conferring SLs insensitivity when mutated. The best sequence identity was with bacterial RsbQ. Both proteins belong to the superfamily of alpha/beta-fold hydrolases, some members of which play a role in the metabolism or signalling of plant hormones. The Dwarf14 (D14) structure was refined by means of molecular dynamics simulations. In order to support the hypothesis that D14 could be an endogenous SLs receptor, we performed docking experiments with a natural ligand., Conclusions: It is suggested that D14 interacts with and thereby may act as a receptor for SLs in plants. This hypothesis offers a starting point to experimentally study the mechanism of its activity in vivo by means of structural, molecular and genetic approaches. Lastly, knowledge of the putative receptor structure will boost the research on analogues of the natural substrates as required for agricultural applications.

A new class of strigolactone analogues has been synthesized. They differ from known molecules, both of natural and synthetic origin, in two main features. The conjugated system extends from the enol ether bridge to the A ring, the B ring is a heterocycle while the C ring is a cyclic ketone instead of a gamma-lactone. The key step of the synthesis is a Nazarov cyclization on activated substrates. Bioassays using Orobanche seeds have revealed that all the molecules strongly stimulate germination; in particular the oxygen containing analogues are the most active. Interestingly, some of the new molecules show fluorescent properties.

The article mentions the active regulation of Strigolactones involving their influx and efflux, also mentioning the cell-trafficking system.

The direct transformation of lactam-, lactone-, and thiolactone-derived triflates into N-methoxy-N-methyl or morpholine Weinreb amides has been realized using Pd-catalyzed aminocarbonylation under CO atmospheric pressure and at room temperature. The carbonylative coupling can be efficiently carried out with 2% of catalyst in the presence of Xantphos as a ligand. The amides smoothly react with nucleophiles to afford acylated aza-, oxa-, and thio-heterocycles. The proposed methodology could be advantageously exploited for the synthesis of dienones in which one of the double bonds is embedded in a heterocyclic moiety, as useful substrates for Nazarov cyclization. [ABSTRACT FROM AUTHOR]