Degraded limonoids: biologically active limonoid fragments re-enhancing interest in Meliaceae and Rutaceae sources

Durán‐Peña, María Jesús; Botubol-Ares, José Manuel; Collado, Isidro González; Hernández-Galán, Rosario

doi:10.1007/s11101-023-09856-1

Cited by 3 publications

(1 citation statement)

References 195 publications

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“…Fraxinellone (4) and congeners (e.g., fraxinellonone and isofraxinellone) have led to the synthesis of derivatives and novel insecticide candidates [23][24][25]. There are also fragmented limonoids, often called degraded limonoids, corresponding to smaller products with ring openings associated with the loss of a skeletal fragment [20]. In general, these smaller molecules are easier to access by chemical synthesis than complex full limonoids, and as such, they provide starting structures for the total or semi-synthesis of natural products or original derivatives derived from naturally occurring limonoids.…”

Section: Introductionmentioning

confidence: 99%

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Vergoten,

Bailly

2024

IJMS

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Limonoids are extremely diversified in plants, with many categories of products bearing an intact, rearranged or fragmented oxygenated scaffold. A specific subgroup of fragmented or degraded limonoids derives from the tetranortriterpenoid prieurianin, initially isolated from the tree Trichilia prieuriana but also found in other plants of the Meliaceae family, including the more abundant species Aphanamixis polystachya. Prieurianin-type limonoids include about seventy compounds, among which are dregeanin and rohitukin. Prieurianin and analogs exhibit insecticidal, antimicrobial, antiadipogenic and/or antiparasitic properties but their mechanism of action remains ill-defined at present. Previous studies have shown that prieurianin, initially known as endosidin 1, stabilizes the actin cytoskeleton in plant and mammalian cells via the modulation of the architecture and dynamic of the actin network, most likely via interference with actin-binding proteins. A new mechanistic hypothesis is advanced here based on the recent discovery of the targeting of the chaperone protein Hsp47 by the fragmented limonoid fraxinellone. Molecular modeling suggested that prieurianin and, to a lesser extent dregeanin, can form very stable complexes with Hsp47 at the protein–collagen interface. Hsp-binding may account for the insecticidal action of the product. The present review draws up a new mechanistic portrait of prieurianin and provides an overview of the pharmacological properties of this atypical limonoid and its chemical family.

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Section: Introductionmentioning

confidence: 99%

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Vergoten,

Bailly

2024

IJMS

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Steroids from the Meliaceae family and their biological activities

Mouthé Happi,

Teufel

2024

Phytochemistry

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In Silico Larvicidal Activity Study of Six Limonoids Against Mosquito Larvae (Aedes aegypti L.) Ecdysone Receptor Protein

Rajab

2024

sciphy

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In an earlier study, six limonoids namely pyroangolensolide, calodendrolide, limonin, limonin diosphenol, harrisonin and pedonin were reported to exhibit varying larvicidal activity against Aedes aegypti L. second instar larvae. The degraded limonoids exhibited a higher larvicidal activity relative to the more complex compounds. To investigate this observation at the relevant Aedes aegypti L. receptor level, the six limonoids were subjected to an in silico docking study to evaluate the binding characteristics of the selected limonoids in the ecdysone receptor (EcR) protein (PDB code 1z5x). This was compared with the binding affinity of the dipteran specific ecdysone agonist, RH 5849 (1,2-Dibenzoyl-1-tert-butylhydrazine). The EcR protein1z5x-LBP was identified from literature data. The binding energies of the ligands docked in the EcR protein 1z5x-LBP ranged from 3.0 to -9.1 kcal/mol and the dissociation constants (Kd) ranged from 2.10×10-7 M to 1.59×10+2 M. RH 5849 had a binding energy of -8.9 kcal/mol which was comparable with those displayed by pyroangolensolide (-9.1 kcal/mol) and calodendrolide (-9.0 kcal mol). Two pharmacophoric factors were important in the observed binding: (a) the hydrogen-bonding interactions by the residues Arg 271, Arg 275 Tyr 296. Thr231 and Ala 286 and (b) the hydrophobic pocket residues Met 268, Met 272, Met 269, Phe 285, and Leu 308. The binding affinities of the selected limonoids in the EcR pocket compared well with the observed larvicidal activity as reported earlier and in the literature. This study offers an opportunity to develop structurally simpler and specific receptor targeted larvicides against Aedes aegypti L.

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Degraded limonoids: biologically active limonoid fragments re-enhancing interest in Meliaceae and Rutaceae sources

Cited by 3 publications

References 195 publications

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Insights into the Mechanism of Action of the Degraded Limonoid Prieurianin

Steroids from the Meliaceae family and their biological activities

In Silico Larvicidal Activity Study of Six Limonoids Against Mosquito Larvae (Aedes aegypti L.) Ecdysone Receptor Protein

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