Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

Wei, Jielu; Ding, Li; Xi, Xin; Liu, Lulu; Zhao, Ximei; Wu, Wenjun; Zhang, Jiwen

doi:10.3390/molecules22101701

Cited by 12 publications

(6 citation statements)

References 29 publications

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“…Our previous works show that the target of celangulin V is the H subunit of V-ATPase in the midgut of M. separata. ,, Thus, to explore the binding mode of target compounds and the V-ATPase H subunit, the molecular docking of compounds 6.16 and 6.19 with the V-ATPase H subunit of M. separata was analyzed. The docking results of compounds 6.16 , 6.19 , and celangulin V are shown in Figure .…”

Section: Results and Discussionmentioning

confidence: 99%

In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity

Qian,

Hu,

Wang

et al. 2024

J. Agric. Food Chem.

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Celangulin V is a novel botanical insecticide with significant bioactivity and a unique molecular target, but its complex polyol ester structure hinders its broader application in agriculture. To discover new analogues of celangulin V with a simpler structure and enhanced biological activities, we initiated a research project aimed at simplifying its structure and assessing insecticidal efficacy. In this study, a series of novel 1-tetralone derivatives were designed via a structure-based rational design approach and synthesized by a facile method. The biological activities of the target compounds were determined against Mythimna separata (M. separata), Plutella xylostella, and Rhopalosiphum padi. The results revealed that most of the synthesized compounds exhibited superior activities compared to celangulin V. Remarkably, the insecticidal activity of compound 6.16 demonstrated 102-fold greater stomach toxicity than celangulin V against M. separata. In addition, certain compounds showed significant contact toxicity against M. separata, a finding not reported previously in the structural optimization studies of celangulin V. Molecular docking analysis illustrated that the binding pocket of compound 6.16 with the H subunit of V-ATPase was the same as celangulin V. This study presents novel insights into the structural optimization of botanical pesticides.

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Section: Results and Discussionmentioning

confidence: 99%

In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity

Qian,

Hu,

Wang

et al. 2024

J. Agric. Food Chem.

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“…The effects on the mitochondrial function of other dihydroagarofuran-type sesquiterpenes have been reported. For example, dihydroagarofuran-type sesquiterpenes polyesters have inhibitor properties in the mitochondrial function by binding to the subunit H of the protein V-ATPase, which affects the digestive system of insects [16,17]. Furthermore, some sesquiterpenoids showed trypanocidal activity by mitochondrial dysfunction and ROS generation, for instance, the sesquiterpenoids isolated from Maytenus boaria generate cytosolic vacuolization, autophagic phenotype, and mitochondrial swelling [16,17].…”

Section: Discussionmentioning

confidence: 99%

“…For example, dihydroagarofuran-type sesquiterpenes polyesters have inhibitor properties in the mitochondrial function by binding to the subunit H of the protein V-ATPase, which affects the digestive system of insects [16,17]. Furthermore, some sesquiterpenoids showed trypanocidal activity by mitochondrial dysfunction and ROS generation, for instance, the sesquiterpenoids isolated from Maytenus boaria generate cytosolic vacuolization, autophagic phenotype, and mitochondrial swelling [16,17]. In conclusion, dihydroagarofuran-type sesquiterpenes, as the ones isolated in the present research, are important natural molecules present in plants of the Maytenus genus, and could be utilized as molecular scaffolds for the development of new anticancer agents that target apoptosis promotion by mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

et al. 2020

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Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. β-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (µg/mL) of 40, 4.7, and 5 µg/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The β-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-β-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 µM, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the β-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction.

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“…ATP6AP2 was discovered to be related to the transmembrane sector of the V-type ATPases. A previous research discovered that the prorenin receptor (PRR) is an element of the Wnt receptor compound and PRR purposes in a reninsovereign way as a connector amid Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) (ATP6AP2) compound [17,18].…”

Section: Effects Of Atp6ap2 On Gastric Cancer Cell Viabilitymentioning

confidence: 99%

MiR-148a-3p suppresses the progression of gastric cancer cells through targeting ATP6AP2

Jin¹,

Cai²,

Shi³

et al. 2020

Trop. J. Pharm Res

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Purpose: Gastric cancer (GC) is one of the most frequent tumors with high mortality rate, worldwide. A proper understanding of the mechanism underlying its progression is required for its diagnosis and development of novel treatment option. MicroRNAs are associated with the development and advancement of different types of cancer, including GC. The current research was aimed at investigating the molecular and biological function of miR-148a-3p in GC development.Methods: A human normal gastric epithelial cell line, GES-1 (control) as well as four GC cell lines (NUGC-4, SNU-520, STKM-2 and MKN-74) were employed for the study. MiR-148a-3p and ATP6AP2 expression levels in GC cell lines were examined by RT-qPCR technique. Transfection procedure was used to upregulate miR-148a-3p expression in the MKN-45 cell line. MTT assay was utilized to evaluate cell viability in GC cell lines. The molecular interaction between miR-148a-3p and ATP6AP2 was predicted using bioinformatics system and the prediction was then validated by luciferase reporter assay.Results: Expression levels of miR-148-3p was low, whilst that of ATP6AP2 was high in GC cell lines. MiR-148a-3p overexpression resulted in the reduction of cell viability in GC cell lines. More so, it was confirmed that miR-148-3p, as a post-transcriptional regulator inhibited ATP6AP2 expression by having a negative association with it in GC cells. More so, ATP6AP2 was found to be a direct target of miR-148a-3p.Conclusion: Our results revealed that miR-148a-3p plays a crucial function in GC development through targeting ATP6AP2. This finding could be explored in the discovery of new therapeutic approaches for GC treatment. Keywords: ATP6AP2, Cell viability, Gastric cancer, miR-148a-3p, Progression

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Molecular Insights into the Potential Insecticidal Interaction of β-Dihydroagarofuran Derivatives with the H Subunit of V-ATPase

Cited by 12 publications

References 29 publications

In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity

In-Depth Structural Simplification of Celangulin V: Design, Synthesis, and Biological Activity

Maytenus disticha Extract and an Isolated β-Dihydroagarofuran Induce Mitochondrial Depolarization and Apoptosis in Human Cancer Cells by Increasing Mitochondrial Reactive Oxygen Species

MiR-148a-3p suppresses the progression of gastric cancer cells through targeting ATP6AP2

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