Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes

Sugawara, Akihiro; Kubo, Masahiko; Hirose, Tomoyasu; Yahagi, Kyoichi; Tsunoda, Noriaki; Noguchi, Yoshihiko; Nakashima, Takuji; Takahashi, Yōko; Welz, Claudia; Mueller, Dennis C.; Mertens, Claudia; Koebberling, Johannes; Ōmura, Satoshi; Sunazuka, Toshiaki

doi:10.1016/j.ejmech.2017.12.031

Cited by 13 publications

(20 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The findings are somewhat disappointing, considering that natural products are a main source of novel drug scaffolds [29], especially for anti-parasitics and antimicrobials. Only one new chemical class has emerged from the scientific literature in the review period, namely that of the open nemadectin analogues [103], and very limited effort seems to have been devoted to exploring the SARs of previously described compounds, with the exception of the jietacins [117]. Most publications analysed are rather preliminary reports of compounds with low to moderate activity from sources not explored before for anthelmintic activity, but yielding in the end already known chemical structures.…”

Section: Discussionmentioning

confidence: 99%

“…Closing this subsection, the SAR of the hydrophobic azoxy compounds jietacins (Fig. 9) has been explored and reported recently [117]. This compound class, produced by Streptomyces bacteria, and its nematocidal activity were first described decades ago by workers at the Kitasato Institute [118], but no reports of chemical development had appeared until 2018.…”

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

“…However, a Chinese institution did obtain local intellectual property (IP) protection for methods to prepare the compounds in 1995 (CN 1027905 C). The SAR study now published by Sugawara et al [117] indicates that a vinyl azoxy group, located at the end of a linear aliphatic chain of 9–14 carbon atoms, is most efficacious in vitro and in vivo . Compounds were tested in vitro for inhibition of motility of xL3 larvae of both Cooperia curticei and H. contortus , and for inhibition of enzyme secretion by adult Nippostrongylus brasilensis .…”

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

“…Compounds were tested in vitro for inhibition of motility of xL3 larvae of both Cooperia curticei and H. contortus , and for inhibition of enzyme secretion by adult Nippostrongylus brasilensis . The most active compounds exhibited complete inhibition in the three assays at concentrations of 1–5 µg/ml (3–16 µM) and showed in vivo efficacy in mice infected with Heligmosomoides polygyrus at 25–100 mg/kg, p.o., q.d., for 4 days [117]. The parent compound, jietacin A, was also efficacious in vivo under the same conditions and, unlike some of the simplified analogues, did not present tolerability issues in mice, although it lacked activity against H. contortus .…”

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

See 3 more Smart Citations

An appraisal of natural products active against parasitic nematodes of animals

Garcia-Bustos

Sleebs

2019

Parasites Vectors

View full text Add to dashboard Cite

Here, the scientific and patent literature on the activities of purified natural compounds has been reviewed, with the aim of assessing their suitability as anthelmintic drug discovery starting points. Only compounds described as active against parasitic nematodes of animals or against the model nematode Caenorhabditis elegans have been analysed. Scientific articles published since 2010 and patents granted from 2000, both inclusive, have been included in this analysis. The results show a scarcity of novel chemical structures, a limited follow-up of compounds disclosed before 2010 and a bias towards the screening of plant products, almost to the exclusion of other sources, when microbial extracts have, historically, provided most starting points for anti-infective drugs. All plant products published in this period were previously known, alerting to the high re-discovery rates of a limited number of chemical classes from this source. The most promising compounds described in the literature reviewed here, namely the linear nemadectin-derivatives, are novel and of bacterial origin. Patented but otherwise unpublished spiroketal structures also appear as interesting scaffolds for future development. The patent literature confirmed that it is possible to patent derivatives of previously known products, making them valid starting points for translational research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

See 2 more Smart Citations

An appraisal of natural products active against parasitic nematodes of animals

Garcia-Bustos

Sleebs

2019

Parasites Vectors

View full text Add to dashboard Cite

show abstract

“…Compound 31 has moderate in vitro nematicidal activity against M. exigua with an LC 50 value of 171 mg/L, and affeic acid 3- O -methyltransferase homodimer may be its target of action . The LC 50 values of compounds 33 and 34 against C. elegans were 0.42 and 0.27 mg/L, respectively. , Compound 33 has only moderate or low acute toxicity, its LD 50 is >300 mg/kg, and it does not exhibit mutagenic effects. Fatty chains may be the necessary active functional group for nematicidal compounds.…”

Section: Chemical Nematicidal Active Compoundsmentioning

confidence: 97%

Chemical Nematicides: Recent Research Progress and Outlook

Chen

Song

2020

J. Agric. Food Chem.

118

View full text Add to dashboard Cite

Plant-parasitic nematodes have caused huge economic losses to agriculture worldwide and seriously threaten the sustainable development of modern agriculture. Chemical nematicides are still the most effective means to manage nematodes. However, the long-term use of organophosphorus and carbamate nematicides has led to a lack of field control efficacy and increased nematode resistance. To meet the huge market demand and slow the growth of resistance, new nematicides are needed to enter the market. The rational design and synthesis of new chemical scaffolds to screen for new nematicides is still a difficult task. We reviewed the latest research progress of nematicidal compounds in the past decade, discussed the structure−activity relationship and mechanism of action, and recommended some nematicidal active fragments. It is hoped that this review can update the recent progress on nematicide discoveries and provide new ideas for the design and mechanism of action studies of nematicides.

show abstract

Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica‐Encaged Ultrasmall Copper Catalysts

et al. 2023

View full text Add to dashboard Cite

Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using costeffective N-methoxyformamide and nitroso compounds over Cu-based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere-encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one-pot synthetic method and first used for the synthesis of azoxy compounds. As compared with copper salt catalysts, the Cu@MSN catalyst exhibited remarkably enhanced catalytic activity and superior recycling stability. Such a Cu@MSN catalyst overcame the inherent drawbacks of low activity, fast deactivation, and difficult recycling of traditional metal salt catalysts in organic reactions. This work provides a green and efficient method for the construction of azoxy compounds and also creates new prospects for the application of nanoporous materials confined metal catalysts in organic synthesis.

show abstract

Jietacins, azoxy antibiotics with potent nematocidal activity: Design, synthesis, and biological evaluation against parasitic nematodes

Cited by 13 publications

References 55 publications

An appraisal of natural products active against parasitic nematodes of animals

An appraisal of natural products active against parasitic nematodes of animals

Chemical Nematicides: Recent Research Progress and Outlook

Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica‐Encaged Ultrasmall Copper Catalysts

Contact Info

Product

Resources

About