Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase

Ceruti, Maurizio; Viola, Franca; Balliano, Gianni; Milla, Paola; Roma, G.; Grossi, Giancarlo; Rocco, Flavio

doi:10.1039/b200888m

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…Furthermore, this design considerably simplifies the synthesis since the primary hydroxyl group is the most nucleophilic function. We thus envisaged to access 6-squalenoyl ascorbic acid (Vit C–SQ) by direct condensation of 1,1′,2-trisnor-squalenic acid, easily available from squalene 31 , 32 , without protection of the tetronic ring. Several synthesis strategies were described to obtained SQ derivatives 33 – 35 .…”

Section: Resultsmentioning

confidence: 99%

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Vitamin C–squalene bioconjugate promotes epidermal thickening and collagen production in human skin

Gref

Deloménie

Maksimenko

et al. 2020

Sci Rep

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Vitamin C (Vit C) benefits to human skin physiology notably by stimulating the biosynthesis of collagen. The main cutaneous collagens are types I and III, which are less synthesized with aging. Vit C is one of the main promotors of collagen formation but it poorly bypasses the epidermis stratum corneum barrier. To address this challenge, we developed a lipophilic version of Vit C for improving skin diffusion and delivery. Vit C was covalently conjugated to squalene (SQ), a natural lipid of the skin, forming a novel Vit C–SQ derivative suitable for cream formulation. Its biological activity was investigated on human whole skin explants in an ex vivo model, through histology and protein and gene expression analyses. Results were compared to Vit C coupled to the reference lipophilic compound palmitic acid, (Vit C–Palmitate). It was observed that Vit C–SQ significantly increased epidermal thickness and preferentially favored collagen III production in human skin after application for 10 days. It also promoted glycosaminoglycans production in a higher extent comparatively to Vit C–Palmitate and free Vit C. Microdissection of the explants to separate dermis and epidermis allowed to measure higher transcriptional effects either in epidermis or in dermis. Among the formulations studied, the strongest effects were observed with Vit C–SQ.

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Section: Resultsmentioning

confidence: 99%

“…Chemicals obtained from commercial suppliers were used without further purification. 1,1′,2-tris-norsqualenic acid was prepare according to Ceruti et al 32 . For comparison purposes, palmitoyl ascorbate was prepared from palmitic acid and ascorbic acid according to litterature 54 .…”

Section: Methodsmentioning

confidence: 99%

Vitamin C–squalene bioconjugate promotes epidermal thickening and collagen production in human skin

Gref

Deloménie

Maksimenko

et al. 2020

Sci Rep

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“…The FTIR spectra highlighted the presence of the characteristic peaks at 2800-3000 cm -1 arising from the C-H stretching of the SQ 27 and the peaks at 1000-1100 cm -1 from the C-O-C vibration of the sugar. 28 The absence of carbonyl band at 1720 cm -1 established that the different final samples didn't contain free SQCHO.…”

Section: Methodsmentioning

confidence: 98%

Squalenoylation of Chitosan: A Platform for Drug Delivery?

et al. 2015

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The present study describes the synthesis of chitosan-squalene (chitosan-SQ), a unique amphiphilic chitosan derivative, which enables the efficient formation of nanoparticles in acetate buffer by self-assembly. The influence of different parameters on the nanoparticle size such as percentage of substitution, pH of the acetate buffer, concentration in chitosan-SQ, and time of stirring was studied. It could be demonstrated that this new polymer was nontoxic to cells, biodegradable, and preserved the anti-infective properties of the initial chitosan.1 Moreover, chitosan-SQ showed good carrier properties by allowing the encapsulation of both hydrophilic and hydrophobic model drug compounds.

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“…C 22 and C 17 squalene aldehyde epoxides 1 and 5 and C 22 and C 17 squalene aldehyde bromohydrins 10 and 12 (Schemes 2 and 3 and Fig. 1) were obtained as previously described (27,37).…”

Section: Methodsmentioning

confidence: 99%

“…Timedependent inactivation of OSC was determined at 37°C as previously described (37). Time-dependent inactivation of SHC was determined at 55°C by adding the inhibitors to enzyme solution in the absence of substrate.…”

Section: Methodsmentioning

confidence: 99%

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Rocco

Bosso

Viola

et al. 2003

Lipids

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Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene (OS) and conjugated and non-conjugated phenylthio derivatives of OS were obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalene-hopene cyclase (SHC) (EC 5.4.99.-), contain the reactive function adjacent to carbons involved in the formation of the third and the fourth cycle during OS cyclization. All the new compounds are inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas most of the phenylthio derivatives were especially active toward SHC.

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Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase

Cited by 7 publications

References 38 publications

Vitamin C–squalene bioconjugate promotes epidermal thickening and collagen production in human skin

Vitamin C–squalene bioconjugate promotes epidermal thickening and collagen production in human skin

Squalenoylation of Chitosan: A Platform for Drug Delivery?

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

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