Structure-activity relationship studies on naphthoquinone analogs. The search for new herbicides based on natural products.

BACKGROUND: Allelopathy and bioassays constitute fundamental tools in the search for new herbicide templates. The work described here is a continuation of a previous study focused on the structure-activity relationships between transport phenomena and phytotoxic activity. Different modifications were made to the naphthoquinone backbone and two key factors were identified as being responsible for changes in activity: lipophilicity and the nature of the functional group. The study of other naturally occurring and semi-synthetic naphthoquinones was also proposed. RESULTS: A total of 12 5-O-acyl plumbagins and 18 analogs with unsaturated and aromatic substituents at positions 2 and 5 were synthesized. These compounds were evaluated in the wheat coleoptile bioassay and against Standard Target Species (STS) and three weeds, namely Echinochloa crus-galli L., Lolium rigidum Gaud. and Lolium perenne L. A strong structure-function relationship was observed for the different naphthoquinones and root and shoot length were the parameters that were most affected. CONCLUSION: Strong inhibitory effects were observed for the isomeric forms 23 and 33 and the derivatives with a free hydroxyl group, i.e. 24 and 30, gave values higher than 70% inhibition for root length in barnyardgrass and perennial ryegrass. These results highlight the potential of these compounds as models in the development of herbicides based on natural products. © 2019 Society of Chemical Industry.

Recent advances in allelopathy for weed control: from knowledge to applications.

Allelopathy is the biological phenomenon of chemical interactions between living organisms in the ecosystem, and must be taken into account in addressing pest and weed problems in future sustainable agriculture. Allelopathy is a multidisciplinary science, but in some cases, aspects of its chemistry are overlooked, despite the need for a deep knowledge of the chemical structural characteristics of allelochemicals to facilitate the design of new herbicides. This review is focused on the most important advances in allelopathy, paying particular attention to the design and development of phenolic compounds, terpenoids and alkaloids as herbicides. The isolation of allelochemicals is mainly addressed, but other aspects such as the analysis and activities of derivatives or analogs are also covered. Furthermore, the use of allelopathy in the fight against parasitic plants is included. The past 12 years have been a prolific period for publications on allelopathy. This critical review discusses future research areas in this field and the state of the art is analyzed from the chemist's perspective. © 2019 Society of Chemical Industry.

Influence of lipophilicity in O-acyl and O-alkyl derivatives of juglone and lawsone: a structure-activity relationship study in the search for natural herbicide models.

BACKGROUND: Naphthoquinones are known for their broad range of biological activities. Given the increasing demands of consumers in relation to food quality and growing concerns about the impact of synthetic herbicides, it is necessary to search for new agrochemicals. Natural products and allelopathy provide new alternatives for the development of pesticides with lower toxicity and greater environmental compatibility. RESULTS: A structure-activity relationship to evaluate the effect of bioavailability was performed. A total of 44 O-acyl and O-alkyl derivatives of juglone and lawsone with different linear chain lengths were prepared. These compounds were tested on etiolated wheat coleoptiles, standard target species (STS) and four weeds, Echinochloa crus-galli L., Lolium rigidum Gaud., Lolium perenne L. and Avena fatua L. The results showed a strong influence of lipophilicity and, in most cases, the data fitted a logP-dependent quadratic mathematical model. CONCLUSION: The effects produced were mostly stunting and necrosis caused by growth inhibition. The potential structure and activity behaviour is described. © 2017 Society of Chemical Industry.

Gibberellic and kaurenoic hybrid strigolactone mimics for seed germination of parasitic weeds.

BACKGROUND: Parasitic weeds are widespread and cause significant losses in important crops. Their germination requires the detection of crop-derived molecules such as strigolactones. Strigolactone mimics are germination-inducing molecules with the potential to apply a suicidal germination strategy for seed bank control of parasitic weeds. RESULTS: The D-ring, which is instrumental in the germination process of seeds of parasitic weeds, was attached to gibberellin (GA3 ) and kaurenoic acid as the scaffold. It was shown that indeed strigolactone mimics prepared from GA3 and kaurenoic acid are active as stimulants when a D-ring is present; some of the mimics are as active as GR24. CONCLUSIONS: The starting molecules were plant hormones that had previous growth-regulating activity in other organisms and the products showed enhanced activity towards parasitic weeds. The information generated may contribute to a better understanding of the germination biochemistry of the weed species used. Further research is required in this area but it is clear that the results are promising. © 2017 Society of Chemical Industry.

Chemical evidence for the effect of Urochloa ruziziensis on glyphosate-resistant soybeans.

BACKGROUND: Soybean (Glycine max) is an important oleaginous legume that has been cultivated in new areas in Brazil, including pastures. Problems of reduced production yields have been reported by soybean growers when the crop is sown immediately after desiccation of pastures of Urochloa spp. using glyphosate. The objective of this work was to extract, isolate and identify the major chemicals from U. ruziziensis that have phytotoxic activity and to evaluate the possible relation between this effect and reduced soybean yield. RESULTS: U. ruziziensis plants at the flowering stage were desiccated using glyphosate at 1.44 kg ha-1 . The plants were collected between five and ten days after treatment. Extracts of dried and ground shoots were obtained by sequential extraction with hexane, dichloromethane and methanol. The results of wheat coleoptile bioassays indicated that the methanol extract was more inhibitory than the dichloromethane extract regardless of glyphosate application. CONCLUSION: Protodioscin, a steroidal saponin, was isolated from the extract as the major component and the activities of this compound were in good agreement with those found for the extract. The release of this compound into the soil is a plausible explanation for the decrease in production observed in transgenic soybean crop after desiccation of U. ruziziensis. © 2017 Society of Chemical Industry.

Phthalimide-derived strigolactone mimics as germinating agents for seeds of parasitic weeds.

BACKGROUND: Broomrapes attack important crops, cause severe yield losses and are difficult to eliminate because their seed bank is virtually indestructible. In the absence of a host, the induction of seed germination leads to inevitable death due to nutrient starvation. Synthetic analogues of germination-inducing factors may constitute a cheap and feasible strategy to control the seed bank. These compounds should be easy and cheap to synthesise, as this will allow their mass production. The aim of this work is to obtain new synthethic germinating agents. RESULTS: Nineteen N-substituted phthalimides containing a butenolide ring and different substituents in the aromatic ring were synthesised. The synthesis started with commercially available phthalimides. The complete collection was assayed against the parasitic weeds Orobanche minor, O. cumana, Phelipanche ramosa and P. aegyptiaca, with the synthetic strigolactone analogue GR24 used as a positive control. These compounds offered low EC50 values: O. cumana 38.3 µM, O. minor 3.77 µM, P. aegyptiaca 1.35 µM and P. ramosa 1.49 µM. CONCLUSIONS: The synthesis was carried out in a few steps and provided the target compounds in good yields. The compounds tested showed great selectivity, and low EC50 values were obtained for structures that were simpler than GR24. © 2016 Society of Chemical Industry.

Aromatic-ring-functionalised benzoxazinones in the system Oryza sativa-Echinochloa crus-galli as biorational herbicide models.

BACKGROUND: Barnyardgrass, Echinochloa crus-galli (L.) Beauv., is one of the most problematic weeds occurring in rice crops. Although efficient chemical control is provided by herbicides available on the market, resistant biotypes provoked by pressure selection have appeared in recent times. This emphasises the need for alternative treatments in which herbicidal compounds from a natural origin could be included. RESULTS: A number of chemicals with a [2H]-1,4-benzoxazin-3(4H)-one (D-DIBOA) skeleton were tested on this weed, and also in rice, in order to achieve an optimal lead for herbicide composition development by taking into consideration phytotoxic effects and selectivity on the weed. 6-Cl-D-DIBOA causes the same effect as the commercial herbicide propanil at a concentration 15 times lower, while 6-F-D-DIBOA causes this inhibition at a dose 30 times lower. The phytotoxicities caused by 8-Cl-D-DIBOA (IC50 = 44 microM, R2 = 0.866) and 7,8-diF-D-DIBOA (IC50 = 52 microM, R2 = 0.9067) are also remarkable. 8-Cl-D-DIBOA was the compound that presented the highest selectivity on Echinochloa crus-galli. The structural requirements for optimal phytotoxicity and selectivity were elucidated by means of QSAR methodology, considering electronic and steric factors. One of the most important descriptors influencing the bioactivity was the dipole moment modulus. This was successfully correlated by employing a second-order polynomial model. CONCLUSION: The in vitro phytotoxic profiles and selectivities shown for these chemicals make them truly promising candidates for higher-level studies. 6F- and 6Cl-D-DIBOA, for their high phytotoxicities, and 8-Cl-D-DIBOA, because of its high selectivity, were found to be the most interesting compounds from this point of view.