Identification of mosquito sterol carrier protein-2 inhibitors

Kim, Min-sik; Wessely, Vilena; Lan, Qing

doi:10.1194/jlr.m400389-jlr200

Cited by 47 publications

(101 citation statements)

References 27 publications

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“…It has been reported that sterol carrier protein-2 inhibitors (SCPIs), including a-mangostin, strongly inhibit the binding between sterol carrier protein-2 (SCP-2) and cholesterol. 6,9) SCPIs selectively inhibited the dietary cholesterol uptake in the midgut and the storage of dietary cholesterol in the fat body in Manduca sexta larvae. 9) In insects, cholesterol is a structural component of the cellular membrane and a precursor of ecdysteroid biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…1), was identified as an SCPI using high throughput screening (HTS), and has shown similar larvicidal activity against mosquito species and the tobacco hornworm. 6,8) Semifield tests have shown that a-mangostin is highly photolytic, 8) suggesting that its environmental residue toxicity would be low. A number of phytochemicals, including neem (Azadirachta indica L.), have shown effective insecticidal activity against some key agricultural pests.…”

Section: Introductionmentioning

confidence: 99%

“…11,12) By inhibiting cholesterol uptake and intracellular transportation, sterol carrier protein-2 inhibitors (SCPIs) exhibited larvicidal activity against several important insect pests, [6][7][8]13) whereas they showed no toxicity against mouse NmuMG cells or rats. 6,8) a-Mangostin, a major xanthone derivative in mangosteen (Garciana mangostana) (Fig. 1), was identified as an SCPI using high throughput screening (HTS), and has shown similar larvicidal activity against mosquito species and the tobacco hornworm.…”

Section: Introductionmentioning

confidence: 99%

“…They have been shown to compete with cholesterol for binding to sterol carrier protein-2 and to reduce cholesterol uptake and cholesterol accumulation in the midgut and fat body. 6,9) Cholesterol is an essential nutrient for development, growth, and reproduction in insects. Due to lack of the enzyme(s) squalene synthase and lanosterol synthase, 10) insects do not synthesize cholesterol de novo, and depend on dietary sources or symbiotic microbes to provide cholesterol for their physiological needs.…”

Section: Introductionmentioning

confidence: 99%

“…5) Sterol carrier protein inhibitors (SCPIs) have shown strong larvicidal activity against mosquito species (Aedes aegypti, Anopheles gambiae, Anopheles quadrimaculatus, Anopheles stephensi, Culex pipiens pipiens, Culex p. quinquefascuatus and Culex restuans) and the tobacco hornworm (Manduca sexta). [6][7][8] Those inhibitors belong to several chemotypes of hydrophobic compounds. They have been shown to compete with cholesterol for binding to sterol carrier protein-2 and to reduce cholesterol uptake and cholesterol accumulation in the midgut and fat body.…”

Section: Introductionmentioning

confidence: 99%

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Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Kim

Lan

2011

J. Pestic. Sci.

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a-Mangostin, a major xanthone derivative in mangosteen (Garcinia mangostana), has been proven to have a wide range of biological-activities. In this study, we assessed the larvicidal and antifeeding activities of a-mangostin using larvae and adults of the Colorado potato beetle, Leptinotarsa decemlineata Say. a-Mangostin showed larvicidal activity and growth inhibitory effects under non-choice feeding conditions. The LC 50 values with 7-, 14-and 23-day treatment were 63.66 (13.29-279.79) mM, 8.37 (2.67-20.27) mM and 4.09 (0.89-11.81) mM, respectively. Larval development was significantly delayed 3-8 days with a-mangostin treatment. The antifeeding activity of a-mangostin was also tested by leaf disc non-choice and choice methods against larvae and adults of L. decemlineata. a-Mangostin had stronger antifeeding-activity toward adults than toward larvae, whereas there was low lethality in adults associated with higher antifeeding indexes (AFIs). The larvicidal and antifeeding effects suggest that a-mangostin and related compounds should be explored for their potential as botanical insecticide alternatives for control of the Colorado potato beetle.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Kim

Lan

2011

J. Pestic. Sci.

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Putative cholesterol‐binding sites in human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5

2012

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Using molecular docking, we identified a cholesterol-binding site in the groove between transmembrane helices 1 and 7 near the inner membrane-water interface of the G protein-coupled receptor CXCR4, a coreceptor for HIV entry into cells. In this docking pose, the amino group of lysine K67 establishes a hydrogen bond with the hydroxyl group of cholesterol, whereas tyrosine Y302 stacks with cholesterol by its aromatic side chain, and a number of residues form hydrophobic contacts with cholesterol. Sequence alignment showed that a similar putative cholesterol-binding site is also present in CCR5, another HIV coreceptor. We suggest that the interaction of cholesterol with these putative cholesterol-binding sites in CXCR4 and CCR5 is responsible for the presence of these receptors in lipid rafts, for the effect of cholesterol on their conformational stability and function, and for the role that cell cholesterol plays in the cell entry of HIV strains that use these membrane proteins as coreceptors. We propose that mutations of residues that are involved in cholesterol binding will make CXCR4 and CCR5 insensitive to membrane cholesterol content. Cholesterol-binding sites in HIV coreceptors are potential targets for steroid drugs that bind to CXCR4 and CCR5 with higher binding affinity than cholesterol, but do not stabilize the native conformation of these proteins.

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NPC1b as a novel target in controlling the cotton bollworm, Helicoverpa armigera

Zheng

Yue

Kuang

et al. 2020

Pest Management Science

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BACKGROUND: Insects cannot synthesize sterols and must acquire them from food. The mechanisms underlying how insects uptake dietary sterols are largely unknown except that NPC1b, an integral membrane protein, has been shown to be responsible for dietary cholesterol uptake in Drosophila melanogaster. However, whether NPC1b orthologs in other insect species, particularly the economically important pests, function similarly remains to be determined. RESULTS:In this study, we characterized the function of NPC1b in Helicoverpa armigera, a global pest that causes severe yield losses to many important crops. Limiting dietary cholesterol uptake to insects significantly inhibited food ingestion and weight gain. Compared to the wild-type H. armigera, the CRISPR/Cas9-edited NPC1b mutant larvae were incapable of getting adequate cholesterol and died in their early life stage. Gene expression profile and in situ hybridization analyses indicated that NPC1b was mainly expressed in the midgut where dietary cholesterol was absorbed. Expression of NPC1b was also correlated with the feeding life stages and was especially upregulated during early larval instars. Protein-ligand docking and sequence similarity analyses further demonstrated that NPC1b proteins of lepidopteran insects shared a relatively conserved cholesterol binding region, NPC1b_NTD, which, however, was highly divergent from bees-derived sequences.CONCLUSION: NPC1b was crucial for dietary cholesterol uptake and growth of H. armigera, and therefore could serve as an insecticide target for the development of a novel pest-management approach to control this economically significant insect pest with little off-target effect on bees and sterol-autotrophic animals.

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Identification of mosquito sterol carrier protein-2 inhibitors

Cited by 47 publications

References 27 publications

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Larvicidal activity of .ALPHA.-mangostin in the Colorado potato beetle, Leptinotarsa decemlineata

Putative cholesterol‐binding sites in human immunodeficiency virus (HIV) coreceptors CXCR4 and CCR5

NPC1b as a novel target in controlling the cotton bollworm, Helicoverpa armigera

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