Structure−Activity Relationship of Polyisoprenyl Benzophenones from <i>Garcinia pyrifera</i> on the Tubulin/Microtubule System

Roux, Delphine Le; Hadi, Hamid A.; Thoret, Sylviane; Guénard, Daniel; Thoison, Odile; Païs, M.; Sévenet, Thierry

doi:10.1021/np0000872

Cited by 84 publications

(96 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, guttiferones A-F were shown to reduce the cytopathic effects in HIV-infected cells. [14] Guttiferone E inhibits the depolymerization of the microtubules into tubulin, [15] and guttiferone I was reported to be a ligand of liver X receptors. [13a] Since SIRT1 is a regulator of HIV transcription [6] and SIRT2 a tubulin deacetylase, [7a] we assayed the isolated guttiferone G for inhibitory activity against sirtuin.…”

Section: Dedicated To Professor Peter Welzel On the Occasion Of His 7mentioning

confidence: 99%

Phloroglucinol Derivatives Guttiferone G, Aristoforin, and Hyperforin: Inhibitors of Human Sirtuins SIRT1 and SIRT2

et al. 2007

View full text Add to dashboard Cite

Section: Dedicated To Professor Peter Welzel On the Occasion Of His 7mentioning

confidence: 99%

Phloroglucinol Derivatives Guttiferone G, Aristoforin, and Hyperforin: Inhibitors of Human Sirtuins SIRT1 and SIRT2

et al. 2007

View full text Add to dashboard Cite

“…1 These compounds can be divided principally into two classes, with type A possessing a bridgehead acyl group adjacent to a quaternary center, and type B having two bridgehead isoprenyl chains and an acyl group bound to C-3. 2 Moreover, irrespective of the type (A or B), some PPAPs have the 7-substituent either in an equatorial exo position (i.e., nemorosone, 2 clusianone, 3 or aristophenone 4 ) or in an axial endo position (i.e., 7-epi-nemorosone 5 or xanthochymol 6 ). Finally, natural products with a tricyclic core, with an oxygen heterocycle, are also found as in the case of garsubellin A 7 or of hyperibone I 8 with their 4-oxa-tricyclo [6.3.1.0 1,5 ]dodec-5-ene-7,12-dione skeletons.…”

Section: Introductionmentioning

confidence: 99%

“…10e Our interest in the field of PPAPs came from the observation that xanthochymol was active in a tubulin disassembly inhibition test. 6 After our work leading to the isolation of oblongifolins A-D, 12 we undertook synthetic studies toward type B PPAPs. 11,13 We previously showed that the boron trifluoride catalyzed Effenberger α,α'-annulation 14 of isomeric 2,4,6-triprenyl-3,3-dimethylcyclohexanones TMS enol ethers 1 with malonyl dichloride allowed the formation of the bicyclo[3.3.1]nonane-2,4,9-trione 2 with an equatorial prenyl group.…”

Section: Introductionmentioning

confidence: 99%

A rapid access to the core skeleton of atypic tricyclic polyprenylated acylphloroglucinols

Delpech¹,

Tolón²,

Marazano³

2010

Arkivoc

View full text Add to dashboard Cite

A synthesis of (4S*,6S*)-2,4,6-triallyl-3,3-dimethylcyclohexanones, and the treatment of their TMS enol ethers with malonyl dichloride in the presence of BF 3 •Et 2 O, are reported. Formation of a ketoacid, resulting from acylation without cyclization, and of a tricyclic phloroglucinol derivative, involving Effenberger annulation with concomitant O-cyclization, were obtained. The tricyclic compound has the core skeleton of the hyperibones H and I, atypical natural polycyclic polyprenylated acylphloroglucinols. Mechanistic and stereochemical aspects are discussed.

show abstract

“…This indicates that compounds 1 and 4 both exhibit antiproliferative characteristics. The antimicrotubule drug docetaxol was used as a control since type B PPAP compounds have been demonstrated to exhibit an inhibitory activity of the tubulin assembly of carcinoma cells [17]. In conclusion, 1 and 4 have potential for development as anticancer candidates, and future works to study their modes of action as antimictrotubule agents should be emphasized.…”

mentioning

confidence: 99%

Structural Derivatization of Clusianone and In Vitro Cytotoxicity Evaluation Targeting Respiratory Carcinoma Cells

2016

View full text Add to dashboard Cite

Abstract! Clusianone (1) was isolated from Garcinia parvifolia and structurally modified using semisynthetic methods to obtain compounds 2-4. The structural derivatization included methylation (2), hydrogenation (3), and the addition of a methylamine group [(4) to (1)]. Cytotoxic effects of these compounds were assessed on MRC5 fibroblasts, A549 lung adenocarcinoma, HK1 squamous nasopharynx carcinoma, and NP69 normal nasopharyngeal epithelial cell lines. Clusianone (1) showed cytotoxic activity against A549 cells with an IC 50 value of 3.06 µM. Compound (4) showed cytotoxic activities against both A549 and HK1 cells with IC 50 values of 4.09 µM and 3.43 µM, respectively. The results of the cytotoxicity assay provide a correlation on the structure activity relationship of clusianone against HK1 and A549 cells, which can be further investigated as a potential antiproliferative compound. Key wordsGarcinia parvifolia · Clusiaceae · clusianone analogues · semisynthetic methods · cytotoxic activity Supporting information available online at http://www.thieme-connect.de/products Natural clusianone belongs to compounds classified as type B polyprenylated polycyclic acylphloroglucines (PPAPs) that are found in plants of the Clusiaceae (Guttiferae) family [1,2]. To date, natural clusianone has been found in various parts of the targeted Clusiaceae plants, including fruits [3], flowers [4,5], leaves [6], roots [7], stems, and bark [8,9]. Naturally occurring 1 has shown potential anticancer activity [9] and further investigations of clusianone-treated HepG2 hepatocarcinoma cells revealed cytotoxic effects by mitochondrial impairment [10]. In the last decade, clusianone (1) has gained substantial interest from the synthetic community leading to a breakthrough in total synthesis of this compound [11][12][13][14]. Synthetic clusianone was tested for cytotoxicity in several cancer cell lines: HeLa (cervix carcinoma), MIAPaCa-2 (pancreatic carcinoma), and MCF7 (breast adenocarcinoma). The IC 50 values ranged from 3.0 µM to 8.3 µM for the three cancer cell lines [15,16]. In our studies, we extracted clusianone using a previously published method [6]. The isolation and abundance of clusianone from the leaves of Garcinia parvifolia (Miq.) Miq. has made chemical modifications readily attainable as compared to clusianone isolated from the dried stem bark of Garcinia assigu [9] and the roots of Hypericum hypericoides (L.) Crantz [7]. X-ray crystallography was identical in previous reports, and a detailed comparison of our and previously reported NMR data [8] was established.This method provided a quantity of over 0.5 g (0.05% yield) of 1 to be used as starting material for synthesizing sufficient quantities of clusianone derivatives (2-4). All products were purified via column chromatography. The products 1-4 exhibited the predicted fragmentation and mass m/z when analyzed by ESI-MS (l " Fig. 1). In addition, further characterizations of 1-4 were conducted utilizing 1 HNMR and 13 CNMR spectroscopy to characterize both tautomers (a/b)...

show abstract

Structure−Activity Relationship of Polyisoprenyl Benzophenones from Garcinia pyrifera on the Tubulin/Microtubule System

Cited by 84 publications

References 24 publications

Phloroglucinol Derivatives Guttiferone G, Aristoforin, and Hyperforin: Inhibitors of Human Sirtuins SIRT1 and SIRT2

Phloroglucinol Derivatives Guttiferone G, Aristoforin, and Hyperforin: Inhibitors of Human Sirtuins SIRT1 and SIRT2

A rapid access to the core skeleton of atypic tricyclic polyprenylated acylphloroglucinols

Structural Derivatization of Clusianone and In Vitro Cytotoxicity Evaluation Targeting Respiratory Carcinoma Cells

Contact Info

Product

Resources

About