Synthesis of 3′-O-Alkyl Homologues and a Biotin Probe of Isorhamnetin and Evaluation of Cytotoxic Efficacy on Cancer Cells

Isorhamnetin is a natural flavonoid which shows a variety of biological activities such as antioxidant, anti-inflammatory and antitumor. In order to identify the cellular binding protein of isorhamnetin as potential anti-cancer target, we first synthesized 3′-O-substituted quercetin as isorhamnetin homologues and evaluated the growth inhibitory activity of these derivatives on breast, colon and prostate cancer cell lines. The preliminary results showed that the 3′-O modification did not affect the cytotoxic activity of the scaffold. Analysis of the co-crystal structure and the docking pose of isorhamnetin with reported binding protein of isorhamnetin or quercetin indicated the 3′-O-substitution groups located outside of the binding pocket, which is in accordance with activity of 3′-O derivatives. Then a biotin conjugate of isorhamnetin with a tetraethylene glycol (PEG)₄ linker at the 3′ position was synthesized and the resulting probe retained the anti-proliferative activity on cancer cell lines, while the cellular fluorescence analysis showed the distribution of probe inside the cells which indicated the probe had limited cell permeability. Finally, pull down assay both in situ inside cells and in the cell lysates indicated the isorhamnetin biotin probe was capable of protein labeling in cell lysates. These findings provide the isorhamnetin 3′-O-biotin probe as a tool to reveal the target proteins of isorhamnetin.     

Pattern partitioning of floral flavonoids in the Mimulus luteus complex

Some flavonoids are differentially distributed between the spots and the background in the flowers of the Mimulus luteus complex; others are not. T     

Leaf flavonoid chemistry and taxonomy of Coreopsis sect. Coreopsis

Seventeen flavonoid glycosides were isolated from the leaves of the nine species of Coreopsis sect. Coreopsis. The compounds include two flavones, four flavonols, a 6-hydroxyflavone, a 6-hydroxyflavonol, two 6-methoxyflavones, a 6-methoxyflavonol and three chalcone-aurone pairs. Chemistry distinguishes all species except C. auriculata and C. intermedia. The mean flavonoid similarity for pair-wise comparison of the four species of annuals (C. basalis, C. nuecensis, C. nuecensoides and C. wrightii) is 0.63 whereas it is 0.66 for the five perennial species (C. auriculata, C. grandiflora, C. intermedia, C. lanceolata, C. pubescens) and 0.54 for comparison of annuals with perennials. This indicates that on the average there is slightly higher flavonoid similarity among species of annuals and among species of perennials than there is between annuals and perennials. Lack of the chalcone-aurone pair coreopsin-sulfurein in perennials is the only consistent chemical difference between annuals and perennials. Leaf flavonoid chemistry supports the hypothesis that C. nuecensis and C. nuecensoides are closely related species but flavonoid data are not concordant with the hypothesis of close relationship between C. basalis and C. wrightii, intermedia, Coreopsis pubescens and C. lanceolata are considered closely related and flavonoid chemistry is concordant with this hypothesis. Coreopsis lanceolata is also viewed as closely allied to C. auriculata, but flavonoids suggest the latter species is more similar to C. intermedia. Coreopsis grandiflora is the only perennial species lacking flavonols and has the fewest number of compounds of any species in the section; chemical data support the view that C. grandiflora is quite distinct from other perennial species of sect. Coreopsis.     

Design,Synthesis, and Docking Study of Quinine-9-Triazolyl Conjugates

To develop a better chemotherapeutically potential candidate for lung cancer treatment and cure with repurposed motifs, quinine has been linked with biocompatible CuAAC-inspired regioselective 1,2,3-triazole linker and a series of ten novel 1,2,3-triazolyl-9-quinine conjugates have been developed by utilizing click conjugation of glycosyl ether alkynes with 9-epi-9-azido-9-deoxy-quinine under standard click conditions. In parallel, the docking study indicated that the resulting conjugates have an overall appreciable interaction with ALK-5 macromolecules. Moreover, the mannose-triazolyl conjugate exhibited the highest binding interactions of −7.6 kcal/mol with H-bond interaction with the targeted macromolecular system and indicate the hope for future trials for anti-lung cancer candidates.     

A 5, 6-dimethoxylated flavone in the leaf resin of Adenostoma sparsifolium

A new flavone 5,6-dimethoxy-3,7,4′-trihydroxyflavone was isolated from the external leaf resin of Adenostoma sparsifolium and identified by spect