Chalcone Dimers Research Articles

Flavonoids dimers from the fruits of Psoralea corylifolia and their cytotoxicity against MCF-7 cells

Nine new flavonoids dimers, psocorylins R-Z (1–9), were isolated from the fruits of Psoralea corylifolia L. (Psoraleae Fructus), a traditional Chinese medicine. The structures of these compounds were elucidated via multiple spectroscopic techniques and X-ray diffraction. Psocorylins R (1) and S (2) were rare cyclobutane-containing chalcone dimers, and psocorylins T-Z (3–9) were established by CC or COC bond of two flavonoid monomers. The structural-types, flavonoids dimers, were isolated from the plant for the first time, enriching the chemical diversity. The cytotoxicity assay suggested that compounds 1, 2, 4, 5, 6 and 8 exhibited cytotoxic activities against MCF-7 cells. Furthermore, compounds 1 and 8 significantly increased intracellular ROS levels, decreased MMP and induced apoptosis of MCF-7 cells. They markedly upregulated the expression of Bax and cleaved caspase-3, and suppressed Bcl-2 and caspase-3 levels, indicating their mechanism of Bcl-2/Bax/Cleaved caspase-3 pathway. Hence, our findings not only promoted the chemical investigation of Psoraleae Fructus, but also provided potential bioactive natural products for anti-cancer.

New dimer and trimer of chalcone derivatives from anti-inflammatory and antinociceptive extracts of Schinopsis brasiliensis roots

Ethnopharmacology relevanceSchinopsis brasiliensis Engl. is an endemic tree of the Brazilian semi-arid regions belonging to the Anacardiaceae family. It is the main representative of the genus Schinopsis, mostly native to Brazil and popularly known as "braúna" or "baraúna". Different parts of this plant are employed in Brazilian folk medicines to treat inflammation in general, sexual impotence, cough, and influenza. Aim of the studyThis work describes the antinociceptive (acetic acid-induced writhing and formalin-induced nociception) and anti-inflammatory (paw edema and neutrophil migration) activities of the extract of the root of S. brasiliensis. Besides, the evaluation of total phenolic compounds and antioxidant, antimicrobial (including MRSA bacteria), and acetylcholinesterase inhibition activities were also determined. Material and methodsThe pure compounds were isolated by different chromatographic techniques and their chemical structures have been unambiguously elucidated based on extensive spectroscopic methods, including 1D (1H, 13C, DEPT, and NOEdiff) and 2D (HSQC, HMBC, and NOESY) NMR experiments, MS data, and comparison with the literature data of similar compounds. The antinociceptive and anti-inflammatory activities were evaluated by acid acetic writhing test, formalin paw edema, and by the investigation of neutrophil migration to the peritoneal cavities of mice. For antimicrobial evaluation were determined MIC and MBC, antioxidant activities were obtained by TPC and DPPH tests, and AChE inhibition by Elmann's methodology. ResultsThe extracts showed antinociceptive and anti-inflammatory activities and two unusual new compounds, a cyclobutanyl chalcone trimer (schinopsone A) and a cyclohexene-containing chalcone dimer (schinopsone B), with six known compounds were isolated from the active extracts. Additionally, the acetylcholinesterase inhibitory activity for isolated compounds was reported for the first time in this study. Molecular docking studies indicated that the isolated compounds are responsible for the interaction with anti-inflammatory targets (COX 1 and 2 and LOX) with variable binding affinities, indicating a possible mechanism of action of these compounds. ConclusionsThese findings indicate for the first time the correlation between the anti-inflammatory activity different enriched polyphenol-organic soluble fractions of S. brasiliensis, and it contributes to the understanding of the anti-inflammatory potential of S. brasiliensis.

Anti-inflammatory Chalcone-Isoflavone Dimers and Chalcone Dimers from Caragana jubata.

Two new chalcone-isoflavone dimers, caraganins A (1) and B (2), two new chalcone dimers, caraganins C (3) and D (4), and eight known compounds (5-12) were obtained from the red heartwood of the rhizomes of Caragana jubata. The structures of caraganins A-D were established by 1D and 2D NMR spectroscopy, HRMS and ECD analysis, and comparison with previously known compounds. The anti-inflammatory activities of the new compounds were evaluated by measuring the production of NO, IL-6, and TNF-α in mouse RAW 264.7 macrophages induced by lipopolysaccharide. Among these, compounds 2 and 4 showed the most potent inhibitory activities (IC50: 4.1 and 5.2 μM, respectively) on nitric oxide formation, and compounds 1 and 4 displayed the most potent inhibitory activities on the secretion of inflammatory factor TNF-α, with IC50 values of 11.4 and 14.7 μM. The possible biosynthetic pathways of the chalcone-isoflavone dimers and the chalcone dimers are proposed.

Structurally Diverse Cytotoxic Dimeric Chalcones from Oxytropis chiliophylla.

Ten isomeric cyclobutane- and cyclohexene-containing chalcone dimers, oxyfadichalcones A-G, were isolated from the aerial parts of Oxytropis chiliophylla. These included six new compounds and three pairs of enantiomers that are being reported from natural sources for the first time. The relative configurations were elucidated by spectroscopic data analysis, while the absolute configurations were determined by comparing the experimental and calculated electronic circular dichroism spectra. Quantitative LC-MS analysis of the main dimers from different parts of the plant revealed their characteristic accumulation in the viscous secretion and provided supporting evidence for the hypothesized photochemical biosynthesis. In addition, the cytotoxic activities of all isolates against the PC-3 human prostate cancer cell line are reported.

Redox and respiratory chain related alterations in the lophirones B and C-mediated bacterial lethality

The influence of chalcone dimers, lophirones B and C on redox status and respiratory chain activity of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa was investigated. Minimum inhibitory concentrations (MIC) of lophirones B and C against E. coli, P. aeruginosa and S. aureus are 200-; 100-; 200- and 150-μg/mL respectively. Similarly, the minimum bactericidal concentrations (MBC) of lophirones B and C are 250; 200; 300 and 200-μg/mL respectively. The optical densities and colony forming units of lophirones B and C-treated bacteria decreased in time-dependent manner. Superoxide anion content of E. coli, P. aeruginosa and S. aureus exposed to lophirones B and C (4× MIC) increased significantly. Superoxide dismutase and catalase in the chalcone dimers-treated bacteria increased significantly. Conversely, reduced glutathione in lophirones B and C-treated bacteria decrease significantly with corresponding increase in glutathione disulfide. Furthermore, malondialdehyde and fragmented DNA increased significantly following exposure to the chalcone dimers. The respiratory complex I and II decreased significantly in the chalcone dimers-treated bacteria. From the findings, lophirones B and C altered intracellular redox status via enhanced oxidant generation possibly by autoxidation, Fenton chemistry and inhibiting electron transport chain resulting to lipid peroxidation and DNA fragmentation and consequentially bacterial cell death.

Lophirones B and C Attenuate Acetaminophen-Induced Liver Damage in Mice: Studies on Hepatic, Oxidative Stress and Inflammatory Biomarkers

Lophirones B and C are chalcone dimers with proven chemopreventive activity. This study evaluates the hepatoprotective effect lophirones B and C in acetaminophen-induced hepatic damage in mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Oral administrations of lophirones B and C significantly (p < 0.05) attenuated acetaminophen-mediated alterations in serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin and total bilirubin. Similarly, acetaminophen-mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6- phosphate dehydrogenase were significantly attenuated in the liver of mice. Increased levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl and fragmented DNA were significantly lowered by lophirones B and C. Levels of tumour necrosis factor-α, interleukin-6 and 8 were significantly lowered in serum of acetaminophen treated mice by the chalcone dimers. Overall, results of this study show that lophirones B and C halted acetaminophen-mediated hepatotoxicity.

The Mesomorphic Properties of Chalcone Dimer Derivatives

A homologous series of symmetrical dimers viz bis (4-n-alkoxy benzoyloxy) α-phenyl β-benzoyl-ethylenes was synthesized and studied with a view to understanding the relation between molecular structure and the mesomorphic behavior. Twelve members of the dimeric series were synthesized, and the methoxy to butyloxy homologues are not liquid crystals, but the pentyloxy to hexadecyloxy are liquid crystals. The pentyl to heptyl dimers are only nematogenic, but the higher homologues show smectogenic mesomorphism prior to nematogenic mesophase formation. The phase diagram of phase transition curves behaves in a normal manner except for the smectic to nematic transition curve which behaves in an unexpected manner. The smectic and nematic thermal stabilities are 103°C and 131.7°C, respectively. The smectogenic and nematogenic phase lengths vary between 17.4°C to 28.3°C and 2.1°C to 29.9°C, respectively. The liquid crystal properties of presently investigated novel chalcone dimers are compared with known monomeric chalcones.

ChemInform Abstract: Oxyfadichalcones A—C: Three Chalcone Dimers Fused Through a Cyclobutane Ring from Tibetan Medicine Oxytropis Falcata Bunge.

AbstractOxyfadichalcones A (I) and B (II) are unprecedented chalcone dimers fused by head‐to‐tail [2 + 2] cycloaddition, that has never been found previously in nature.

Exploration, synthesis and studies of gel forming simple sugar-chalcone derivatives

Simple sugar-chalcone derivatives have been obtained by aldol condensation where aglycon–chalcone dimer was obtained as an unexpected product in addition to the sugar-chalcone

ChemInform Abstract: New Chalcone Dimers (I) from Caesalpinia ferrea Mart Act as Potent Inhibitors of DNA Topoisomerase II.

ChemInform Abstract: New Chalcone Dimers (I) from Caesalpinia ferrea Mart Act as Potent Inhibitors of DNA Topoisomerase II.

Two structurally distinct chalcone dimers from Helichrysum zivojinii and their activities in cancer cell lines

Dimers tomoroside A (1) and tomoroside B (2) of the co-occuring known chalcone monomer (3), along with the seven known flavonoid glucosides (4–10), were isolated from the aerial parts of Helichrysum zivojinii Černjavski & Soška. The structures of the isolated compounds were elucidated by spectroscopic techniques. Compound 1 inhibited topo IIα and hif-1α expression and stimulated doxorubicin anticancer effect, while 2 increased the expression of hif-1α, probably acting as antioxidant and redox status modulator. Notably, 2 synergized with Tipifarnib showing potential to improve the action of this new chemotherapeutic involved in the modulation of mitogene activated protein (MAP) kinase signaling pathway.

Oxyfadichalcones A–C: three chalcone dimers fused through a cyclobutane ring from Tibetan medicine Oxytropis falcata Bunge

Oxyfadichalcones A and B, two unprecedented chalcone dimers fused through a cyclobutane ring by head-to-tail [2+2] cycloaddition of two chalcones that had never been found previously in nature, along with oxyfadichalcone C, a new head-to-head [2+2] cyclized chalcone dimer, were simultaneously obtained from Oxytropis falcata. Structural elucidation was succeeded by spectroscopic and single-crystal synchrotron radiation analysis. Additionally, the photosynthesis of the chalcone dimers was performed and the plausible biosynthesis was discussed.

Cytotoxic, Antimutagenic, and Antioxidant Activities of Methanolic Extract and Chalcone Dimers (Lophirones B and C) Derived From Lophira alata (Van Tiegh. Ex Keay) Stem Bark

The cytotoxic, antimutagenic, and antioxidant activities of methanolic extract and lophirones B and C derived from Lophira alata stem bark were evaluated. The extract and lophirones B and C significantly (P < .05) reduced the viability of Ehrlich ascites carcinoma cells. There were concentration-dependent reduction in 4-nitro-o-aminophenylenediamine and benzo[a]pyrene-induced frame shift mutation as well as aflatoxin B1-induced base pair substitution by the extract and lophirones B and C. The extract and lophirones B and C concentration dependently scavenged DPPH radical, superoxide anion radical, hydrogen peroxide, hydroxyl radicals, and reduced ferric ion in the potassium hexacyanoferrate III reducing system. The results obtained from this study revealed that methanolic extract and lophirones B and C derived from Lophira alata stem bark posses anticancer, antimutagenic, and antioxidant activities, with lophirone C producing the best anticancer, antimutagenic, and antioxidant activities. The acclaimed anticancer activity of Lophira alata may be attributed to lophirones B and C.

Electrophilic and Reactive Oxygen Species Detoxification Potentials of Chalcone Dimers is Mediated by Redox Transcription Factor Nrf‐2

Nuclear erythroid related factor-2 (Nrf2), a redox-transcription factor, plays a critical role in the detoxification of electrophilic and reactive oxygen species that halt various biochemical and molecular processes. This makes it a candidate for regulation by polyphenols. This study investigates the capability of chalcone dimers (lophirones B and C) to induce expressions and activities of cytoprotective enzymes. Chalcone dimers administration to rats not only induced the Nrf2, but also suppressed cytoplasmic Kelch-like ECH-associated protein 1 (Keap1) expressions. In addition, the chalcone dimers significantly (p < 0.05) increased the expressions and activities of nicotinamide adenine dinucleotide and reduced quinone oxidoreductase-1, glutathione-S-transferase, epoxide hydrolase and uridyl glucuronosyl transferase in rat liver. Also, activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in rat liver increased significantly (p < 0.05). Overall, lophirones B and C increased the expressions and activities of cytoprotective proteins in rat liver possibly through the reduction of cytoplasmic Keap1 expression, leading to the nuclear translocation of Nrf2.

New chalcone dimers from Caesalpinia ferrea Mart act as potent inhibitors of DNA topoisomerase II

New chalcone dimers, pauferrol B ( 2 ), and pauferrol C ( 3 ), were isolated from the stems of Caesalpinia ferrea Mart, and their structures were determined on the basis of 2D NMR spectroscopy. These new chalcone dimers showed potent inhibitory activities against human topoisomerase II and cell proliferation via the induction of apoptosis in human leukemia HL 60 cells. Absolute configurations of 2 and 3 were estimated by the comparison of CD spectra with a dihydrobenzofuran derivative 4 , which was enantioselectively synthesized from 2-hydroxyphenyl acetic acid.

Chalcone Oligomers from Brackenridgea zanguebarica

The genus Brackenridgea belongs to the family Ochnaceae and consists of approximately 12 species distributed from Africa to the Fiji Islands. Brackenridgea zanguebarica has been used as a traditional African medicine for the treatment of wounds, conjunctivitis and anemia. Various chalcone dimers have been reported from this family. These dimers are of interest due to the inconsistent isomers that result from chalcone framework. Herein, we report the isolation of two new dimeric (1 and 2) and one new tetrameric chalcones (3) along with four known compounds. Their structures were elucidated through spectroscopic methods, including NMR experiments and MS spectra analyses.

Chalcone Oligomers from the Stem Bark of Brackenridgea zanguebarica

The genus Brackenridgea belongs to the family Ochnaceae with approximately 12 species distributed from Africa to the Fiji Islands [1]. B. zanguebarica has been used as a traditional African medicine for the treatment of wounds [2], conjunctivitis [3] and anaemia [4]. Previously, various chalcone dimers have been isolated from this family, such as calodenin B [5], isochamaejasmine [5, 6], and brackenin [6]. These dimers are of interest due to the inconsistent isomers that result from the many chalcone frameworks. Phytochemical investigation of the stem bark of B. zanguebarica is indicated to explore new chemical constituents. Structure elucidation resulted in the isolation of four dimeric and one tetrameric chalcones including three new compounds.

Two-photon-induced cycloreversion reaction of chalcone photodimers

The photocleavage reaction of chalcone photodimers has been studied using a two-photon process. For this purpose, a novel chalcone dimer has been synthesized as a low molecular weight model substance for polymer bound chalcones and its photochemistry triggered by two-photon-absorption (2PA) has been investigated using a pulsed frequency-doubled Nd:YAG-laser. The 2PA-induced cycloreversion reaction selectively leads to the cleavage of the chalcone photodimers resulting in the formation of monomeric chalcone molecules. Hence, as an application chalcones can be used as a photosensitive linker which can be cleaved beyond an UV-absorbing barrier. The 2PA cross section of the chalcone photodimer was determined to be of 1.1 × 10 −49 cm 4 s photon −1 (11 GM).

Natural product chemistry in north-eastern Brazil.

The north-eastern region of Brazil comprises about one third of the country's territory. It is a semi-arid region with a flora rich in aromatic, toxic and medicinal plants. Screening of aromatic plants led to the investigation of about 2000 samples of essential oil from plants from the region and from abroad. Studies done by the Universidade Federal do Ceará and other research groups in the region discovered several new substances with distinct pharmacological activities. Recent examples are: schultezin, hydroxy-bisabolol, trans-annonene, (-)-hardwickic acid, trans-cascarillone, nor-cucurbitacins, oleanolic saponin and chalcone dimer. A social programme called the Living Pharmacy was created to teach poor people how to cultivate and use medicinal plants correctly. A project to develop interaction between the university and industry also arose from these studies.

Isolation and synthesis of analgesic and anti-inflammatory compounds from Ochna squarrosa L.

Two new furanoflavonoids ( 1, 2), one new chalcone dimer ( 3) along with six known compounds, chrysophanol, 5- O-methyl squarrosin, 5-methoxy furano[4″,5″,6,7]flavone, calodenone, lophirone A and lophirone H were isolated from the ethyl acetate-soluble fraction of methanol extract of root bark of Ochna squarrosa. Chrysophanol, calodenone, lophirone A and lophirone H were isolated from this plant for the first time. The structures of all the isolated compounds were confirmed by 1D and 2D spectroscopic data. These compounds were tested for analgesic and anti-inflammatory activity. All the new compounds showed good analgesic and anti-inflammatory activity. A simple and facile method for the cleavage of benzyl ethers using I 2 in trigol is also reported.