106115-49-5

Upstream product

• 120-14-9 3,4-dimethoxy-benzaldehyde 
• 120-92-3 cyclopentanone 

Downstream Products

• 1392494-92-6 7'-(3,4-dimethoxybenzylidene)-4'-(3,4-dimethoxyphenyl)-4',5',6',7'-tetrahydro-2'H-spiro[cyclopentane-1,3'-cyclopenta[b]pyran]-2'-one 
• 1392494-97-1 7'-(3,4-dimethoxybenzylidene)-4'-(3,4-dimethoxyphenyl)-4',5',6',7'-tetrahydro-2'H-spiro[cyclohexane-1,3'-cyclopenta[b]pyran]-2'-one 
• 115592-06-8 (E)-1,3-Bis(2-(3,4-dimethoxyphenyl)methyl-5-(3,4-dimethoxyphenyl)methylen-1-cyclopentenyl)propen 

Relevant academic research and scientific papers

Curcumin analogs as potent aldose reductase inhibitors

In the present study, curcuminoids isolated from curcuma longa were demonstrated to possess inhibitory activities on bovine lens aldose reductase. In order to find more potent aldose reductase inhibitor, curcumin analogs were synthesized and evaluated for their ability to inhibit bovine lens aldose reductase enzyme. The results indicated that the compounds with tetrahydroxyl groups, 2,6-bis(3,4-dihydroxybenzylidene)cyclohexanone (A2), 2,5-bis(3,4-dihydroxybenzylidene)cyclopentanone (B2), 1,5-bis(3,4-dihydroxyphenyl)-1,4-pentadiene-3-one (C2), and 3,5-bis(3,4-dihydroxybenzylidene)-4-piperidone (D2) showed remarkably potent inhibitory effects on aldose reductase with IC50 of 2.9 μM, 2.6 μM, 3.4 μM, and 4.9 μM, respectively. The structure-activity relationship revealed that the curcumin analogs with ortho-dihydroxyl groups could form a more tight affinity with aldose reductase to exert more potential inhibitory activities.

Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro. Most of these compounds showed good synergistic activities against C. tropicalis. Among them, compound 9 exhibited significant synergistic activities against Candida spp. SARs were also discussed. In particular, a cell growth test exhibited that a combination of 1 μg ml-1 fluconazole and 64 μg ml-1 or 128 μg ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis. The synergistic effect may be associated with the changes of the intracellular ATP content and cell membrane permeability. Our results provided a basis for future evaluation and development of these compounds as leads for therapeutics for fluconazole-resistant candidiasis.

Synthesis, structure, electrochemistry, and photophysics of 2,5-dibenzylidenecyclopentanones containing in benzene rings substituents different in polarity

A series of cross-conjugated dienones was synthesized to study the dependence of physicochemical characteristics on the nature of substituents in the aromatic groups of symmetric cyclopentanone dibenzylidene derivatives. The structure of compounds was established by electronic, IR, and NMR spectroscopy and X-ray diffraction study. All the compounds obtained possess the E,E-geometry. In the crystalline state, the arrangement of the dienone molecules is unfavorable for the intermolecular [2+2] photocycloaddition to take place. The low-temperature phases transition for unsubstituted diphenyl derivative of cyclopentanone was detected using variable-temperature X-ray diffraction and differential scanning calorimetry. Oxidation and reduction potentials of the dienones were measured by cyclic voltammetry. Their dependence on the nature and placement of substituents in the benzene rings was demonstrated. A linear correlation (R = 0.9343) between the difference of electrochemical oxidation and reduction potentials and the energy of the long-wavelength absorption maximum was found, that allows us to recommend the use of the data obtained in the correlation analysis of other compounds of this class.

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.

Synthesis and evaluation of curcumin-related compounds for anticancer activity

Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3, Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC50 for these compounds was lower than 1 μM in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity.

CURCUMIN ANALOGS AND METHODS OF USE THEREOF

Curcumin analogs and methods of use thereof are provided.

A facile synthesis of α,α′-(EE)-bis(benzylidene)-cycloalkanones and their antitubercular evaluations

An economical and facile synthesis of α,α′-(EE)-bis(benzylidene)-cycloalkanones was achieved by the reaction of cycloalkanones with different aromatic aldehydes using ethanolic KOH in good yields. Few of the selected compounds were reduced with NaBH4 to the respective α,α′-(EE)-bis(benzylidene)-cycloalkanols. All these compounds and our earlier synthesized cyclohexyl phenyl methanols were evaluated for their antitubercular, antifungal and antibacterial activities. Several compounds displayed moderate antitubercular activity with MIC = 12.5-1.56 μg/mL. However, none of the compounds displayed any significant antifungal activity.

Amine-catalyzed aldol condensation in the presence of lithium perchlorate

A catalytic aldol condensation in the presence of lithium perchlorate and tertiary amines is described giving pure products in high yields. The aldol condensation can be performed even in the presence of hydrated lithium perchlorate. Georg Thieme Verlag Stuttgart.

α-Glucosidase inhibition of natural curcuminoids and curcumin analogs

Natural curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) isolated from Curcuma longa (turmeric), and synthetic curcumin analogs (A 1-7, B1-7, C1-6 and D1-7) were evaluated in vitro for the α-glucosidase inhibitory activity via UV and circular dichroism (CD) spectroscopy. The results indicated that natural curcuminoid compound 3 showed a remarkable inhibitory effect with IC 50 of 23.0 μM, and the synthetic compounds A2, B 2, C2 and D2 showed potent inhibitory effects with IC50 of 2.8, 2.6, 1.6 and 8.2 μM, respectively. Kinetic study exhibited that the mechanism of α-glucosidase inhibition of both 3 and C2 was non-competitive. The structure activity relationship revealed that the ortho dihydroxyl groups could form a more tight interaction with α-glucosidase to exert more potential inhibitory activities.