7249-34-5

Usage

Molecular Structure

2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone is a derivative of cyclopentanone with two benzylidene groups, each attached to a hydroxy and a methoxy group.

Reactivity

The presence of hydroxy and methoxy groups makes the compound highly reactive, making it a potential precursor for the synthesis of various organic molecules and polymers.

Antioxidant Properties

The presence of phenolic groups in the compound indicates potential antioxidant properties, which could have implications in the development of pharmaceuticals or health supplements.

Potential Applications

Due to its unique structure and properties, 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone has potential applications in the fields of medicine and materials science.

Upstream product

• 121-33-5 vanillin 
• 120-92-3 cyclopentanone 
• 91471-08-8 3-methoxy-4-(tetrahydropyran-2-yloxy)benzaldehyde 
• 123-08-0 4-hydroxy-benzaldehyde 
• 946161-27-9 C₃₁H₃₆O₇ 

Downstream Products

• 834912-92-4 2,5-bis(4-acetoxy-3-methoxybenzylidene)cyclopentanone 
• 51728-79-1 2,5-divanillyl-cyclopentanone 

Relevant academic research and scientific papers

Vanillin-derived epoxy monomer for synthesis of bio-based epoxy thermosets: effect of functionality on thermal, mechanical, chemical and structural properties

Abstract: Tri-functional vanillin-derived epoxy monomer was developed through the synthesized di-functional reagent and cured with a series of different types of hardeners (hydroxyl and amine based) to evaluate thermo-mechanical properties of the resultan

Diarylidenecyclopentanone derivatives as potent anti-inflammatory and anticancer agents

Cancer is often associated with chronic inflammation. In order to develop potential anticancer and anti-inflammatory agents a series of 26 diarylidenecyclopentanones (DACPs) Ia–Iv, II, III, and IV were synthesized. Five of the synthesized DACPs are novel (Ih, Ij, Ik, Is, and Iv), derivative Iv was characterized using single-crystal X-ray diffraction study. All the synthesized derivatives were tested for their anti-inflammatory as well as cytotoxicity properties. Compound Is is found to have the highest anti-inflammatory activity (93.67%) by inhibiting PGE2 (prostaglandin E2) production. Three of the DACPs (Io, It, and Iu) were observed to have high cytotoxicity with IC50 value of 8.73 ± 0.06 μM (Io), 12.55 ± 0.31 μM (It), and 11.47 ± 0.15 μM (Iu) against HeLa cells. Further staining and cell cycle analysis was done using these three DACPs to understand their mechanism of action. The G0/G1 phase was observed to be the longest one through which the cells undergo apoptosis.

Inhibition of dengue virus by curcuminoids

The dengue virus is considered to be a globally important human pathogen prevalent in tropical and subtropical regions of the world. According to a recent estimate, the disease burden due to DENV infections is ～390 million infections per year globally in ～100 countries including the southern US, Puerto Rico and Hawaii, resulting in nearly ～25,000 deaths mostly among children. Despite the significant morbidity and mortality that results from DENV infections, there is currently no effective chemotherapeutic treatment for DENV infections. We identified curcumin as an inhibitor of DENV2 NS2B/NS3protease in a previous high-throughput screening (HTS) campaign. We synthesized four analogues of curcumin (curcuminoids) and tested the in vitro protease inhibition activity and inhibition of replication by cell-based assays. The results revealed that curcumin is a weak inhibitor of the viral protease. However, the analogues exhibited more potent inhibition of DENV infectivity in plaque assays suggesting that the cellular pathway(s) required for viral replication and/or assembly are targeted by these compounds. Further analysis shows that inhibition of genes involved in lipid biosynthesis, and of actin polymerization by curcuminoids, are likely to be involved as their mode of action in DENV2-infected cells. Three of the curcumin derivatives possess good selectivity indices (SI) (>10) when compared to the parent curcumin.

Curcumin and a hemi-analogue with improved blood–brain barrier permeability protect against amyloid-beta toxicity in Caenorhabditis elegans via SKN-1/Nrf activation

Objectives: This study aims to investigate the blood–brain barrier (BBB) permeability of curcumin analogues with shortened linkers and their ability to protect against amyloid-beta toxicity in a whole organism model. Method: Four curcumin analogues were synthesized. These analogues and curcumin were evaluated for their BBB permeability in the parallel artificial membrane permeability assay. The transgenic Caenorhabditis elegansGMC101 that expresses human Aβ1–42 was treated with the compounds to evaluate their ability to delay Aβ-induced paralysis. Expression of skn-1mRNA was examined on nematodes treated with selected efficacious compounds. In vitro Aβ aggregation in the presence of the compounds was performed. Key findings: The four analogues showed improved BBB permeability vs curcumin in the PAMPA with the hemi-analogue C4 having the highest permeability coefficient. At 100 μm, analogues C1 and C4 as well as curcumin significantly prolonged the survival of the nematodes protecting against Aβ toxicity. However, only curcumin and C4 showed protection at lower concentrations. skn-1mRNA was significantly elevated in nematodes treated with curcumin and C4 indicating SKN-1/Nrf activation as a possible mode of action. Conclusions: Analogue C4 provides a new lead for the development of a curcumin-based compound for protection against Aβ toxicity with an improved BBB permeability.

Solvent-free catalytic preparation of 2,6-dibenzylidenecycloalkanones using 2-hydroxyethylammonium acetate ionic liquid as catalyst

Various 2,6-dibenzylidenecycloalkanones were readily prepared in a condensation reaction catalyzed by 2-hydroxyethylammonium acetate ionic liquid under solvent-free conditions in excellent yields. The major advantages of the present method are high yields, short reaction times, lack of solvent, simplicity of performance, and low cost. Graphical abstract: [Figure not available: see fulltext.]

Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

Osteosarcoma is a primary bone malignancy with aggressive metastatic potential and poor prognosis rates. In our earlier work we have investigated the therapeutic potential of curcumin as an anti-invasive agent in osteosarcoma by its ability to regulate the Wnt/β-catenin signaling pathway. However, the clinical use of curcumin is limited owing to its low potency and poor pharmacokinetic profile. In this study, an attempt was made to achieve more potent Wnt inhibitory activity in osteosarcoma cells by carrying out synthetic chemical modifications of curcumin. We synthesized a total of five series consisting of 43 curcumin analogs and screened in HEK293T cells for inhibition of β-catenin transcriptional activity. Six promising analogs, which were 6.5- to 60-fold more potent than curcumin in inhibiting Wnt activity, were further assessed for their anti-invasive activity and Wnt inhibitory mechanisms. Western blot analysis showed disruption of β-catenin protein nuclear translocation following treatment with analogs 2f, 3c and 4f. Using transwell assays, we also found that these compounds were more potent than 1a (curcumin) in impeding the invasion of osteosarcoma cells, possibly through suppressing MMP-9 activity. Structure-activity-relationship studies revealed that Wnt inhibitory effects could be enhanced by shortening and restraining the flexibility of the 7-carbon linker moiety connecting the terminal aromatic rings of curcumin and substituting both rings with appropriate substituents. Our results demonstrate that the synthesized curcumin analogs are more potent Wnt inhibitors in osteosarcoma cell lines as compared to parental curcumin and are good lead compounds for further development. Future in vivo tests with these compounds will define their therapeutic potentials as promising drug candidates for clinical treatment of osteosarcoma.

Design and synthesis of dimethylaminomethyl-substituted curcumin derivatives/analogues: Potent antitumor and antioxidant activity, improved stability and aqueous solubility compared with curcumin

A series of dimethylaminomethyl-substituted curcumin derivatives/analogues were designed and synthesized. All compounds effectively inhibited HepG2, SGC-7901, A549 and HCT-116 tumor cell lines proliferation in MTT assay. Particularly, compounds 2a and 3d showed much better activity than curcumin against all of the four tumor cell lines. Antioxidant test revealed that these compounds had higher free radical scavenging activity than curcumin towards both DPPH and galvinoxyl radicals. Furthermore, the aqueous solubility and stability of the target compounds were also significantly improved compared with curcumin.

Synthesis and evaluation of DPPH and anti-inflammatory activities of 2,6-bisbenzylidenecyclohexanone and pyrazoline derivatives

A series of thirty three 2,6-bisbenzylidenecyclohexanone and pyrazoline derivatives were synthesized and evaluated for inhibitory activities on IFN-γ/LPS-activated RAW 264.7 cells and DPPH radical scavenging activity. Compounds 8, 9, and 11a demonstrated significant NO inhibitory activity as compared to L-NAME and curcumin with IC50 values of 6.68 ± 0.16, 6.09 ± 0.46, and 6.84 ± 0.12 μM, respectively. Apparently the suppression upon NO secretion was not due to cell death since the active compounds did not reduce the cell viability in close proximity to the IC 50 of NO inhibition. Overall, incorporation of pyrazoline ring as part of the linker chain improved cell viability compared to the 2,6-bisbenzylidenecyclohexanone derivatives. Meanwhile, compound 11 (IC 50 = 13.27 ± 1.78 μM) bearing ortho hydroxyls on the aromatic rings recorded the highest radical scavenging activity as compared with quercetin (IC50 = 21.46 ± 0.85 μM). Springer Science+Business Media, LLC 2010.

Density functional theory studies on 2,5-bis(4-hydroxy-3- methoxybenzylidene)cyclopentanone

The optimized molecular structure, vibrational frequencies, corresponding vibrational assignments of 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone (BHMBC) have been investigated by using density functional theory (B3LYP) methods at 6-311G(d,p) bas

Synthesis, crystal structure and anti-inflammatory properties of curcumin analogues

Curcuminoids have been reported to possess multifunctional bioactivities, especially the ability to inhibit proinflammatory induction. Since it has been suggested that the seven-carbon β-diketone linker in curcumin is responsible for its instability, nine mono-carbonyl five-carbon linker containing analogues were designed and synthesized. Their bioactivity against lipopolysaccharide-induced TNF-α amd IL-6 secretion was evaluated by using mouse J774.1 macrophages. The results showed that the 3′-methoxyl plays an important role in bioactivity and cyclohexanone containing analogues exhibited stronger inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently the most active analogue 3c was determined using single-crystal X-ray diffraction. X-ray analysis and comparison with curcumin reveals that the presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in the enol tautomer in curcumin, may play an important role in the bioactivity. It is suggested that five-carbon linker analogues containing a cyclohexane ring which are synthetically assessable may be pharmacologically important.