Isocucurbitacin D

Lipid-Lowering Activities of Cucurbitacins Isolated from Trichosanthes cucumeroides and Their Synthetic Derivatives.[Pubmed:33269591]

J Nat Prod. 2020 Dec 24;83(12):3536-3544.

In the ongoing efforts to discover natural cholesterol-lowering compounds, dihydrocucurbitacin B, isolated from Trichosanthes cucumeroides roots, was found to promote LDL uptake by upregulating LDLR protein in a PCSK9-dependent process. In this study, an in-depth investigation of T. cucumeroides roots afforded 27 cucurbitacins (1-27), including seven new cucurbitacins (1-7), and their structures were elucidated by spectroscopic data analyses. In order to gain insight into their structure-activity relationship, cucurbitacin derivatives (B1-11 and DB1-11) were synthesized. Evaluation of lipid-lowering activities of these cucurbitacins by an LDL uptake assay in HepG2 cells revealed that most of the compounds improved the LDL uptake rate, among which hexanorIsocucurbitacin D (6) and Isocucurbitacin D (21) exhibited the highest activities (rates of 2.53 and 2.47, respectively), which were comparable to that of the positive control, nagilactone B (rate of 2.07). According to a mechanistic study by Western blot analysis, compounds 6 and 21 dose-dependently increased LDLR protein levels and reduced PCSK9 protein levels, representing promising new lipid-lowering drug candidates.

Cucurbitacin D Is a Disruptor of the HSP90 Chaperone Machinery.[Pubmed:25756299]

J Nat Prod. 2015 Apr 24;78(4):873-9.

Heat shock protein 90 (Hsp90) facilitates the maturation of many newly synthesized and unfolded proteins (clients) via the Hsp90 chaperone cycle, in which Hsp90 forms a heteroprotein complex and relies upon cochaperones, immunophilins, etc., for assistance in client folding. Hsp90 inhibition has emerged as a strategy for anticancer therapies due to the involvement of clients in many oncogenic pathways. Inhibition of chaperone function results in client ubiquitinylation and degradation via the proteasome, ultimately leading to tumor digression. Small molecule inhibitors perturb ATPase activity at the N-terminus and include derivatives of the natural product geldanamycin. However, N-terminal inhibition also leads to induction of the pro-survival heat shock response (HSR), in which displacement of the Hsp90-bound transcription factor, heat shock factor-1, translocates to the nucleus and induces transcription of heat shock proteins, including Hsp90. An alternative strategy for Hsp90 inhibition is disruption of the Hsp90 heteroprotein complex. Disruption of the Hsp90 heteroprotein complex is an effective strategy to prevent client maturation without induction of the HSR. Cucurbitacin D, isolated from Cucurbita texana, and 3-epi-Isocucurbitacin D prevented client maturation without induction of the HSR. Cucurbitacin D also disrupted interactions between Hsp90 and two cochaperones, Cdc37 and p23.

[Studies on chemical constituents in roots of Helicteres angustifolia].[Pubmed:21842648]

Zhongguo Zhong Yao Za Zhi. 2011 May;36(9):1193-7.

OBJECTIVE: To study the chemical constituents of the roots of Helicteres angustifolia. METHOD: The compounds were isolated and purified by column chromatographic methods on silica gel, Sephadex LH-20, ODS and preparative HPLC. Their structures were elucidated on the basis of physicochemical properties and spectral data. RESULTS: Fourteen compounds were isolated from this plant. Their structures were identified as methyl helicterate(1),3-acetoxybetulin(2),3beta-acetoxy-27-(p-hydroxyl)benzoyloxylup-20( 29)-en-28-oic acid methyl ester(3),3beta-acetoxy-27-benzoyloxylup-20(29)-en-28-oic acid(4),3beta-acetoxybetulinic acid(5),pyracrenic acid(6),cucurbitacin D(7),cucurbitacin B(8),Isocucurbitacin D(9),3beta-acetoxy-27-[(4-hydroxybenzoyl)oxy]olean-12-en-28-oic acid methyl ester (10),beta-sitosterol(11),2alpha,7beta,20alpha-trihydroxy-3beta,21-dimethoxy-5-pre gnene(12), hexadecanoic acid(13), and daucosterol(14), respectively. CONCLUSION: Compounds 5,8,9,13, 14 were isolated from this plant for the first time.

A new cucurbitacin from Bolbostemma paniculatum Franguent.[Pubmed:17454317]

J Asian Nat Prod Res. 2007 Mar;9(2):187-90.

A new cucurbitacin with an unusual ring A, Isocucurbitacin D 25-O-acetate (1), was isolated from Bolbostemma paniculatum Franguent together with one known compound, cucurbitacin E (2). The structure of new compound was established by spectroscopic methods.

Cucurbitacins fromCucurbita texana: Evidence for the role of isocucurbitacins.[Pubmed:24248508]

J Chem Ecol. 1993 Jan;19(1):29-37.

In addition to cucurbitacins E andI, cucurbitacins D,1, 3-epi-Isocucurbitacin D,2, and B,3, were isolated from the fruits ofCucurbita texana and structurally identified by UV, IR,(1)H NMR,(13)C NMR, and MS, and 2-O-Beta-glucopyranosylcucurbitacin I was identified. These compounds have not been reported previously as constituents of this species. The isolation of 3-epi-Isocucurbitacin D2 together with normal cucurbitacins suggests that isocucurbitacins occur naturally. Evidence is also discussed that isocucurbitacins are biosynthesized one step ahead of normal cucurbitacin.

[Studies on the constituents of trichosanthes root. III. Constituents of roots of Trichosanthes bracteata Voigt].[Pubmed:2760813]

Yakugaku Zasshi. 1989 Apr;109(4):265-70.

From the fresh roots of Trichosanthes bracteata Voigt., the following substances were identified: methyl palmitate, palmitic acid, suberic acid, alpha-spinasterol, stigmast-7-en-3 beta-ol, alpha-spinasterol 3-O-beta-D-glucopyranoside, stigmast-7-en-3 beta-ol 3-O-beta-D-glucopyranoside, glyceryl 1-palmitate, glyceryl 1-stearate, bryonolic acid, cucurbitacin B, isocucurbitacin B, 3-epi-isocucurbitacin B, 23,24-dihydrocucurbitacin B, 23,24-dihydroisocucurbitacin B, 23,24-dihydro-3-epi-isocucurbitacin B, cucurbitacin D, Isocucurbitacin D and D-glucose. This root contains more than 6 times cucurbitacin of the root of T. kirilowii Maxim. var. japonicum Kitam.