Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans

He, Da-Hai; Slebodnick, Carla; Rakotondraibe, L. Harinantenaina

doi:10.1016/j.bmcl.2017.02.067

Cited by 23 publications

(16 citation statements)

References 15 publications

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“…Further modifications of 1 were implemented to prepare a derivative potentially exhibiting mosquito toxicity without antifeedant activity. We had previously shown that the carbon at C-9 bearing a hydroxyl in capsicodendrin (4), could be transformed into a ketone by treatment with pyridinium chlorochromate 43 . Therefore, in order to produce a dihydroquinone, 1 was reacted with 5 equivalents of the MeMgBr to alkylate the C-12 aldehyde and to cleave off the C-6 acetyl group providing an isomeric mixture of deacetylated lactols 12α-methyl-pereniporin A and 12ß-methyl-pereniporin A (12) (Scheme 3).…”

Section: Derivatization Of Cinnamodialmentioning

confidence: 99%

Semi-synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti

Manwill

Kalsi

et al. 2019

Preprint

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The Aedes aegypti mosquito serves as a major vector for viral diseases, such as dengue, chikungunya, and Zika, which are spreading across the globe and threatening public health. In addition to increased vector transmission, the prevalence of insecticideresistant mosquitoes is also on the rise, thus solidifying the need for new, safe and effective insecticides to control mosquito populations. We recently discovered that cinnamodial, a unique drimane sesquiterpene dialdehyde of the Malagasy medicinal plant Cinnamosma fragrans, exhibited significant larval and adult toxicity to Ae. aegypti and was more efficacious than DEET -the gold standard for insect repellents -at repelling adult female Ae. aegypti from blood feeding. In this study several semisynthetic analogues of cinnamodial were prepared to probe the structure-activity relationship (SAR) for larvicidal, adulticidal and antifeedant activity against Ae. aegypti. Initial efforts were focused on modification of the dialdehyde functionality to produce more stable active analogues and to understand the importance of the 1,4-dialdehyde and the α,ßunsaturated carbonyl in the observed bioactivity of cinnamodial against mosquitoes. This study represents the first investigation into the SAR of cinnamodial as an insecticide and repellent against the medically important Ae. aegypti mosquito. Scheme 1. Derivatization of 1 into structural analogues. Reagents and conditions: (a) NaClO 2 , NaH 2 PO 4 •H 2 O, H 2 O 2 , MeCN, H 2 O, r.t., 24 h; (b) TMS-CHN 2 , MeOH:Et 2 O, 0 o C, 30 min;( c) H 2 N-NH 2 , CH 2 Cl 2 :EtOH, 2 h; (d) MeOH, r.t.; (e) HOCH 2 CH 2 OH, p-TsOH, benzene, reflux, 24 h. Scheme 2. Synthesis of lactols 8 and 9, and formation of 10 from lactol 9. Reagents and conditions: (a) 1 eq. MeMgBr, THF, 78 o C, 2 h; (b) CDCl 3 , 22 d. Scheme 3. Synthesis of 1,4-dione 13. Reagents and conditions: (a) 5 eq. MeMgBr, THF, 78 o C, 2 h; (b) 3.3 eq. PCC, DCM, 0 o C → r.t., 2h. Scheme 4. Reaction mechanism of the reaction of 1 with L-cysteine methyl ester via a cationic azomethine (A) to form the pyrrolidine (16).

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Section: Derivatization Of Cinnamodialmentioning

confidence: 99%

Semi-synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti

Manwill

Kalsi

et al. 2019

Preprint

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“…Both CDIAL and CMOS are active in a remarkable variety of bioassays. In particular, they: 1) inhibit α-glucosidase activity [ 17 , 18 ]; 2) are cytotoxic to various cancer cell lines [ 18 , 20 – 22 ]; 3) are antifungal [ 23 ]; and 4) exhibit vanilloid-like activity [ 24 , 25 ]. In addition, CDIAL inhibits: 1) growth of murine leukemia cells, human T-lymphocytes, and bacteria [ 17 , 26 ]; 2) mammalian inflammatory mechanisms [ 27 ]; and 3) feeding activity of lepidopteran pests [ 16 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti

et al. 2018

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Plants produce various secondary metabolites that offer a potential source of novel insecticides and repellents for the control of mosquito vectors. Plants of the genus Cinnamosma are endemic to, and widely-distributed throughout, the island of Madagascar. The barks of these species are commonly used in traditional medicines for treating a wide range of maladies. The therapeutic nature of the bark is thought to be associated with its enrichment of pungent drimane sesquiterpenes, which elicit antifeedant and toxic effects in some insects. Here we test the hypothesis that a bark extract of Cinnamosma fragrans (CINEX) and its major drimane sesquiterpenes are insecticidal, antifeedant, and repellent to Aedes aegypti, the principal mosquito vector of chikungunya, dengue, yellow fever, and Zika viruses. We demonstrate that CINEX is 1) toxic to larval and adult female mosquitoes, and 2) antifeedant and repellent to adult female mosquitoes. Moreover, we show that cinnamodial (CDIAL), a sesquiterpene dialdehyde isolated from CINEX, duplicates these bioactivities and exhibits similar toxic potency against pyrethroid-susceptible and -resistant strains of Ae. aegypti. Importantly, we show that CDIAL is an agonist of heterologously-expressed mosquito Transient Receptor Potential A1 (TRPA1) channels, and the antifeedant activity of CDIAL is dampened in a TRPA1-deficient strain of Ae. aegypti (TRPA1-/-). Intriguingly, TRPA1-/- mosquitoes do not exhibit toxic resistance to CDIAL. The data indicate that modulation of TRPA1 is required for the sensory detection and avoidance of CDIAL by mosquitoes, but not for inducing the molecule’s toxicity. Our study suggests that CDIAL may serve as a novel chemical platform for the development of natural product-based insecticides and repellents for controlling mosquito vectors.

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“…The carbazole alkaloids are considered to be the main anti-cancer components of the genus Clausena [6,7,44,45,46]. However, several reports demonstrated that the analogs of aromatic glycosides [47,48] and sesquiterpene glycosides [49] also possessed a certain degree of anti-cancer activity. Therefore, it is suggested that some glycosides from this plant probably play a role in the anticancer activity of C. lansium to some extent.…”

Section: Resultsmentioning

confidence: 99%

Phytochemical Study of Stem and Leaf of Clausena lansium

Peng

et al. 2019

Molecules

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Clausena lansium Lour. Skeels (Rutaceae) is widely distributed in South China and has historically been used as a traditional medicine in local healthcare systems. Although the characteristic components (carbazole alkaloids and coumarins) of C. lansium have been found to possess a wide variety of biological activities, little attention has been paid toward the other components of this plant. In the current study, phytochemical analysis of isolates from a water-soluble stem and leaf extract of C. lansium led to the identification of 12 compounds, including five aromatic glycosides, four sesquiterpene glycosides, two dihydrofuranocoumarin glycosides, and one adenosine. All compounds were isolated for the first time from the genus Clausena, including a new aromatic glycoside (1), a new dihydrofuranocoumarin glycoside (6), and two new sesquiterpene glycosides (8 and 9). The phytochemical structures of the isolates were elucidated using spectroscopic analyses including NMR and MS. The existence of these compounds demonstrates the taxonomic significance of C. lansium in the genus Clausena and suggests that some glycosides from this plant probably play a role in the anticancer activity of C. lansium to some extent.

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Bioactive drimane sesquiterpenoids and aromatic glycosides from Cinnamosma fragrans

Cited by 23 publications

References 15 publications

Semi-synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti

Semi-synthetic Cinnamodial Analogues: Structural Insights into the Insecticidal and Antifeedant Activities of Drimane Sesquiterpenes Against the Mosquito Aedes aegypti

A natural agonist of mosquito TRPA1 from the medicinal plant Cinnamosma fragrans that is toxic, antifeedant, and repellent to the yellow fever mosquito Aedes aegypti

Phytochemical Study of Stem and Leaf of Clausena lansium

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