Synthesis and in vitro antifungal activity of new Michael-type amino derivatives of xanthatin, a natural sesquiterpene lactone from Xanthium strumarium L.

Zhi, Xiaoyan; Song, Lili; Liang, Jing; Wei, Siqi; Li, Yang; Yuan, Zhongwei; Hao, Xiaojuan; Hui, Cao; Yang, Chun

doi:10.1016/j.bmcl.2021.128481

Cited by 11 publications

(13 citation statements)

References 19 publications

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“…Xanthatin ( 1 ) had been widely reported as the main antimicrobial component among all the xanthanolides, which had been recognized as an important precursor for the bio-mimic synthesis in exploring the novel antimicrobial agents. Zhi et al, synthesized a series of Michael type amino derivatives from xanthatin ( 1 ) and investigated their antifungal activities against several phytopathogenic fungi, and led to the finding of the more effective ompounds than xanthatin [ 78 ]. In 2009, Liu et al, reported that the water extracts of X. strumarium exhitbited antiviral activity against duck hepatitis B virus and xanthatin ( 1 ) exerted significant activity against influenza A virus [ 79 ].…”

Section: The Biological Activity Of Xanthanolidesmentioning

confidence: 99%

Xanthanolides in Xanthium L.: Structures, Synthesis and Bioactivity

et al. 2022

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Xanthanolides were particularly characteristic of the genus Xanthium, which exhibited broad biological effects and have drawn much attention in pharmacological application. The review surveyed the structures and bioactivities of the xanthanolides in the genus Xanthium, and summarized the synthesis tactics of xanthanolides. The results indicated that over 30 naturally occurring xanthanolides have been isolated from the genus Xanthium in monomeric, dimeric and trimeric forms. The bioassay-guided fractionation studies suggested that the effective fractions on antitumor activities were mostly from weak polar solvents, and xanthatin (1) was the most effective and well-studied xanthanolide. The varieties of structures and structure-activity relationships of the xanthanolides had provided the promising skeleton for the further study. The review aimed at providing guidance for the efficient preparation and the potential prospects of the xanthanolides in the medicinal industry.

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Section: The Biological Activity Of Xanthanolidesmentioning

confidence: 99%

Xanthanolides in Xanthium L.: Structures, Synthesis and Bioactivity

et al. 2022

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“… , Previous reports have found that this natural small-molecule exhibits not only a wide range of important pharmacological activities including anticancer, anti-inflammatory, antioxidant, and neuroprotective activities − but also impressive inhibitory activity against pathogenic microorganism, , which has great potential application in agrochemicals. Therefore, as a part of our efforts to discover novel fungicides from plant secondary metabolites, − several well-known antifungal fragments (e.g., oxadiazole, triazole, or imidazole) (Figure ) were introduced on the framework of ABL to enhance its antifungal effect (Figure ). This study aimed to obtain potent antifungal derivatives from ABL with potential application value.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Natural Sesquiterpene Lactone 1-O-Acetylbritannilactone Analogues Bearing Oxadiazole, Triazole, or Imidazole Scaffolds for the Development of New Fungicidal Candidates

Zhi

Yuan

et al. 2023

J. Agric. Food Chem.

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In recent decades, natural products have been considered important resources for developing of new agrochemicals because of their novel architectures and multibioactivities. Consequently, herein, 1-O-acetylbritannilactone (ABL), a natural sesquiterpene lactone from Inula britannica L., was used as a lead for further modification to discover fungicidal candidates. Six series of ABL-based derivatives containing an oxadiazole, triazole, or imidazole moiety were designed and synthesized, and their antifungal activities were also evaluated in vitro and in vivo. Bioassay results revealed that compounds 8d, 8h, and 8j (EC50 = 61.4, 30.9, and 12.4 μg/mL, respectively) exhibited more pronounced inhibitory activity against Fusarium oxysporum than their precursor ABL (EC50 > 500 μg/mL) and positive control hymexazol (EC50 = 77.2 μg/mL). Derivatives 8d and 11j (EC50 = 19.6 and 41.5 μg/mL, respectively) exhibited more potent antifungal activity toward Cytospora mandshurica than ABL (EC50 = 68.3 μg/mL). Compound 10 exhibited excellent and broad-spectrum antifungal activity against seven phytopathogenic fungal mycelia. Particularly, the inhibitory activity of compound 10 against the mycelium of Botrytis cinerea was more than 10.8- and 2.3-fold those of ABL and hymexazol, respectively. Meanwhile, derivative 10 (IC50 = 47.7 μg/mL) displayed more pronounced inhibitory activity against the spore of B. cinerea than ABL (IC50 > 500 μg/mL) and difenoconazole (IC50 = 80.8 μg/mL). Additionally, the in vivo control efficacy of compound 10 against B. cinerea was further studied using infected tomatoes (protective effect = 58.4%; therapeutic effect = 48.7%). The preliminary structure–activity relationship analysis suggested that the introduction of the 1,3,4-oxadiazole moiety (especially the 1,3,4-oxadiazole heterocycle containing the 4-chlorophenyl, 2-furyl, or 2-pyridinyl group) on the skeleton of ABL was more likely to produce potential antifungal compounds. These findings pave the way for further design and development of ABL-based derivatives as potential antifungal agents.

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“…Therefore, structural optimization of xanthatin has also become a hotspot in recent years. , Meanwhile, our group has prepared Michael-type amino/thiol analogues by the modification of the exo -methylene group of the five-membered ring of xanthatin and found several promising derivatives with potential antifungal effect in a previous work (Figure ). , However, there are few reports related to the modification of unsaturated side chains of the seven-membered ring of xanthatin and their antifungal activity so far. Consequently, encouraged by our previous research results and together with the continuation of our efforts to develop novel agrochemicals derived from the plant NPs, , several series of derivatives modified on the unsaturated side chain of the seven-membered ring of xanthatin were designed and prepared in this work, including the introduction of arylpyrazole, arylimine, thio-acylamino, oxime ether/ester, or other well-known antifungal structural fragments into xanthatin (Figure ).…”

Section: Introductionmentioning

confidence: 99%

“… , However, there are few reports related to the modification of unsaturated side chains of the seven-membered ring of xanthatin and their antifungal activity so far. Consequently, encouraged by our previous research results and together with the continuation of our efforts to develop novel agrochemicals derived from the plant NPs, , several series of derivatives modified on the unsaturated side chain of the seven-membered ring of xanthatin were designed and prepared in this work, including the introduction of arylpyrazole, arylimine, thio-acylamino, oxime ether/ester, or other well-known antifungal structural fragments into xanthatin (Figure ). Furthermore, the in vitro and in vivo inhibitory activities of the synthesized compounds against plant pathogenic fungi were evaluated.…”

Section: Introductionmentioning

confidence: 99%

Natural Sesquiterpene Lactone as Source of Discovery of Novel Fungicidal Candidates: Structural Modification and Antifungal Activity Evaluation of Xanthatin Derived from Xanthium strumarium L

Yang

Yuan

et al. 2023

J. Agric. Food Chem.

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As part of our ongoing efforts to discover novel agricultural fungicidal candidates from natural sesquiterpene lactones, in the present work, sixty-three xanthatin-based derivatives containing a arylpyrazole, arylimine, thio-acylamino, oxime, oxime ether, or oxime ester moiety were synthesized. Their structures were well characterized by 1 H and 13 C nuclear magnetic resonance and high-resolution mass spectrometry, while the absolute configurations of compounds 5′ and 6a were further determined by singlecrystal X-ray diffraction. Meanwhile, the antifungal activities of the prepared compounds against several phytopathogenic fungi were investigated using the spore germination method and the mycelium growth rate method in vitro. The bioassay results illustrated that compounds 5, 5′, and 15 exhibited excellent inhibitory activity against the tested fungal spores and displayed remarkable inhibitory effects on fungal mycelia. Compounds 5 and 5′ exhibited more potent inhibitory activity (IC 50 = 1.1 and 24.8 μg/mL, respectively) against the spore of Botrytis cinerea than their precursor xanthatin (IC 50 = 37.6 μg/mL), wherein the antifungal activity of compound 5 was 34-fold higher than that of xanthatin and 71-fold higher than that of the positive control, difenoconazole (IC 50 = 78.5 μg/mL). Notably, compound 6′a also demonstrated broad-spectrum inhibitory activity against the four tested fungal spores. Meanwhile, compounds 2, 5, 8, and 15 showed prominent inhibitory activity against the mycelia of Cytospora mandshurica with the EC 50 values of 2.3, 11.7, 11.1, and 3.0 μg/mL, respectively, whereas the EC 50 value of xanthatin was 14.8 μg/mL. Additionally, compounds 5′ and 15 exhibited good in vivo therapeutic and protective effects against B. cinerea with values of 55.4 and 62.8%, respectively. The preliminary structure−activity relationship analysis revealed that the introduction of oxime, oxime ether, or oxime ester structural fragment at the C-4 position of xanthatin or the introduction of a chlorine atom at the C-3 position of xanthatin might be significantly beneficial to antifungal activity. In conclusion, the comprehensive investigation indicated that partial xanthatin-based derivatives from this study could be considered for further exploration as potential lead structures toward developing novel fungicidal candidates for crop protection.

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Synthesis and in vitro antifungal activity of new Michael-type amino derivatives of xanthatin, a natural sesquiterpene lactone from Xanthium strumarium L.

Cited by 11 publications

References 19 publications

Xanthanolides in Xanthium L.: Structures, Synthesis and Bioactivity

Xanthanolides in Xanthium L.: Structures, Synthesis and Bioactivity

Discovery of Natural Sesquiterpene Lactone 1-O-Acetylbritannilactone Analogues Bearing Oxadiazole, Triazole, or Imidazole Scaffolds for the Development of New Fungicidal Candidates

Natural Sesquiterpene Lactone as Source of Discovery of Novel Fungicidal Candidates: Structural Modification and Antifungal Activity Evaluation of Xanthatin Derived from Xanthium strumarium L

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