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Growth And Secondary Metabolites Production In Cultured Cells Of Liverworts
Published in R. N. Chopra, Satish C. Bhatla, Bryophyte Development: Physiology and Biochemistry, 2019
Yoshimoto Ohta, Kenji Kato, Reiji Takeda
Most liverworts contain various types of aromatic compounds which are sometimes important as chemosystematic indicators.59 Among them, lunularic acid (7), a dihydrostilbene carboxylic acid, has drawn our attention because of its ubiquitous occurrence exclusively in liverworts (with the exception of one angiosperm species, Hydrangea macrophylla60,61) and because of its proposed role as an endogenous growth regulator (a dormancy factor) in liverworts.60,62,63 Production of lunularic acid was examined in suspension-cultured cells of M. polymorpha and some other species of the Jungermanniales such as J. subulata, Lophocolea heterophylla, and Calypogeia granulata.64 All of the cultured cell lines examined yielded a considerable amount of lunularic acid upon extraction with acetone and column purification of the strong acid fraction. This showed that the production of lunularic acid was a characteristic of cultured cells of liverworts as well as the intact plants. However, the amount of lunularic acid obtained from the cultured cells varied considerably depending on the extraction procedures employed. For example, extraction of M. polymorpha cells with boiling methanol containing 1% acetic acid gave 4.4 μg of lunularic acid per milligram dry weight of cells, whereas only 0.39 μg was obtained upon methanol extraction without acetic acid. This value further decreased to 0.12 μg by extraction with 60% acetonitrile in water under sonication at 4°C.65 A similar effect of extraction methods on the efficiency of obtaining lunularic acid from intact liverworts has been described by Gorham,61 who noticed that lunularic acid was extracted more efficiently by methanol containing hydrochloric acid instead of boiling ethanol. These results suggested the existence of a labile compound. This labile compound, prelunularic acid (8), was isolated from suspension-cultured cells of M. polymorpha.66-61 Filter-harvested cells were extracted with 90% methanol, and successive column chromatography of the extract on Sephadex® LH-20, reverse-phase silica gel, and cellulose columns afforded prelunularic acid, which was directly converted into lunularic acid upon treatment with diluted sulfuric acid or sodium hydroxide solution, or even under neutral conditions (although at a slower rate). Prelunularic acid is a cyclization product of p-coumaryl β-triketo acid and is the first example of a prearomatic intermediate in the phenylpropanoid-polymalonate pathway. This compound is a plausible immediate precursor of lunularic acid.
The potential of nitisinone for the treatment of alkaptonuria
Published in Expert Opinion on Orphan Drugs, 2019
Nitisinone is a naturally occurring herbicide discovered when observations were made of the reduction in the number of other plants growing in close-proximity to the bottlebrush plant (Callistemon) [39]. The absence of other species from around the bottlebrush suggested an effect from inhibition of pathway(s) affiliated with growth. It was discovered that the chemical known as Leptospermone, which is present in the soil around the plants had a bleaching effect, amongst others, on neighboring plants. Leptospermone belongs to the triketone family and impedes chloroplast development by 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibition; HPPD is an enzyme involved in the catabolism of tyrosine and is integral to the production of a number of natural plant products [40,41]. The discovery of the triketone family, of which Leptospermone was an early finding, led to the discovery and development of nitisinone. The initial work in understanding how nitisinone worked was undertaken by Zeneca Agrochemicals following indications that it inhibited the actions of another enzyme which uses tyrosine as a substrate; tyrosine hydroxylase. Further work on nitisinone by Zeneca Central Toxicology Laboratories clarified that Nitisinone did not inhibit tyrosine hydroxylase or tyrosine aminotransferase, but in fact, was a potent inhibitor of HPPD [38].
Usnic acid and its derivatives for pharmaceutical use: a patent review (2000–2017)
Published in Expert Opinion on Therapeutic Patents, 2018
Olga A. Luzina, Nariman F. Salakhutdinov
The most numerous group of UA derivatives are enamine-type compounds, obtained by the reaction of the carbonyl group of UA with primary amines [29]. In this case, the double bonds of the UA ‘triketone’ moiety move with the loss of the acidic proton. Such a modification of the ‘triketone’ fragment of the UA leads to a significant reduction in the properties of the compounds as membrane uncouplers and the loss of toxicity, confirmed in experiments in vitro. Other than enamines, UA derivatives are less frequently mentioned in the literature; however, compounds of different structural types are also found among them. Among the derivatives modified on ring A, whose activity is patented, the most highly represented group is that of derivatives with thiazole and annealed to aromatic ring furanone fragments. Such compounds are obtained through the bromo derivative of UA (Br-UA) (Figure 2), a significant intermediate compound on the way to numerous UA analogs [29].