DrugRep: an automatic virtual screening server for drug repurposing.

Computationally identifying new targets for existing drugs has drawn much attention in drug repurposing due to its advantages over de novo drugs, including low risk, low costs, and rapid pace. To facilitate the drug repurposing computation, we constructed an automated and parameter-free virtual screening server, namely DrugRep, which performed molecular 3D structure construction, binding pocket prediction, docking, similarity comparison and binding affinity screening in a fully automatic manner. DrugRep repurposed drugs not only by receptor-based screening but also by ligand-based screening. The former automatically detected possible binding pockets of the receptor with our cavity detection approach, and then performed batch docking over drugs with a widespread docking program, AutoDock Vina. The latter explored drugs using seven well-established similarity measuring tools, including our recently developed ligand-similarity-based methods LigMate and FitDock. DrugRep utilized easy-to-use graphic interfaces for the user operation, and offered interactive predictions with state-of-the-art accuracy. We expect that this freely available online drug repurposing tool could be beneficial to the drug discovery community. The web site is http://cao.labshare.cn/drugrep/ .

Taste compounds generation and variation of broth in pork meat braised processing by chemical analysis and an electronic tongue system.

The aim was to unveil the generation and variation rule of the main taste components in braised broth for 10 quantitative repeated braising cycles. The major taste compounds of three groups (MS, broth cooked with meat and spices; M, broth cooked with meat; and S, broth cooked with spices) were systematically analyzed by the state-of-art chromatography and electronic sensory technology. As braising cycles progressed, contents of free 5'-nucleotides and amino acids were increased in MS and M, while those nucleotides were not detected in S. A significant discrimination of taste in MS and M was revealed by electronic tongue evaluation during the process. As the formation rates (FR) of taste compounds and the transformation rates (TR) of taste compounds to volatile compounds were mainly accounting for the generation and variation of flavor in broth, a hypothesis was proposed to illustrate the whole variation of taste compounds in the process integrally that the ratio of FR/TR dividing the process into three stages, Degradation, Balance, and Accumulation. PRACTICAL APPLICATIONS: The traditional braising process and formula are empirical and extensive, which impede the increase in meat products output. Nowadays, the industry of braising products is facing a problem of standardization and quality control, and needs to carry out scientific and quantitative process improvement efficiently. Therefore, the developed comprehensive approach demonstrates great potential for braised meat broth flavor monitoring and quality control in an objective and holistic manner. It provides data support and new ideas of technology development for quality control in the process of meat braising.

Leucandioxoles A and B, two 1,3-benzodioxole derivatives from the South China Sea sponge Leucandra sp.

Two new 1,3-benzodioxole derivatives, leucandioxoles A and B (1-2), together with two known related compounds (3-4), have been isolated from the South China Sea sponge Leucandra sp. The structures of all compounds were clearly elucidated on the basis of spectroscopic analyses and compared with the literatures. The cytotoxicity against A549, Hep G2, MDA-MB-231, and HeLa cell lines of 1-4 were evaluated. Only compound 1 exhibited moderate activity against MDA-MB-231 cells with the IC50 value of 7.98 ± 0.74 µM.

Micro-nano particle formation and transformation mechanisms of broth in meat braised processing.

The formation and transformation mechanisms of micro-nano particles (MNPs) in broth during meat braising were systematically investigated through a sophisticated controlled process. Dynamic changes in the morphology, composition and spatial distribution of MNPs were comprehensively characterized, and subsequently the mechanisms were visually uncovered from microcosmic-spatial perspectives. MNPs formed as circular-shape colloidal systems with an aggrandizing tendency for particle number and size and gradually stabilize eventually. Specifically, the major MNPs gradually increased the size from <400 nm to ~1500 nm and accumulated triglycerides and glycoconjugates resulting from lipid oxidation, Maillard reaction, etc. Continuous formation of MNPs in broth progressively facilitated the spatial coalescence and self-assembly of free substances driven by intermolecular interactions, and consequently principal nutrients and flavor compounds further accumulated in the MNPs by the braising process. Hence, this work not only revealed the MNP formation and transformation mechanisms but offered a foundation for investigating MNP-dependent effect on broth flavor.

Integrated recognition and quantitative detection of starch in surimi by infrared spectroscopy and spectroscopic imaging.

Surimi products have become increasingly-consumed food with prominent characteristics of high nutrition and convenience and its supply falls short of demand. However, due to exhausted fishery resource in recent years, surimi adulteration, such as addition of plant proteins, starch and other animal origin meat, is becoming serious, so recognition of these exogenous substances has become an urgent issue. In this study, Fourier transform infrared spectroscopy (FT-IR) combined with infrared spectroscopic imaging could distinguish heterogeneity in surimi qualitatively and quantitatively and obtain integral chemical images so that spatial distribution of each component in surimi could be visually displayed, thus a rapid recognition method and a prediction model were developed. The different starch contents in surimi had been primarily identified through intensity change of infrared absorption peaks at 1045cm-1 and 988cm-1, specifically with peak shifts to 1041cm-1 and to 992cm-1, respectively. In infrared imaging analysis, principal components (PCs) were separated and one key PC was confirmed as starch by characteristic peaks comparison at 1147cm-1, 1075cm-1, 997cm-1 and 930cm-1. Meanwhile, an established statistic model could predict starch content in surimi correctly with a reliable correlation coefficient (R=0.9856) and root mean square error of prediction (RMSEP=5.64). Therefore, FT-IR combined with infrared spectroscopic imaging could be applicable to integrally recognize and quantitatively detect starch in surimi.

A rapid analytical and quantitative evaluation of formaldehyde in squid based on Tri-step IR and partial least squares (PLS).

Formaldehyde abuse for retaining squid freshness is detrimental to public health. The aim is to establish a rapid and quantitative detection method of formaldehyde in squid for screening massive samples. A linear relationship between formaldehyde concentration in squid and formaldehyde concentration in squid soaked water was observed using HPLC. Chemical profile variances of squids were rapidly analyzed by Tri-step infrared spectroscopy. Specifically, with increasing formaldehyde concentration, peak intensities of 2927cm-1 (vas(CH2)), 1081cm-1 (glycogen), 1631cm-1 (ß-sheet proteins) decreased while 1655cm-1 (α-helix proteins) increased. Spectral curve-fitting results further disclosed that ß-sheet proteins were transformed to α-helix and ß-turn conformations. Furthermore, a quantitative prediction model based on IR spectra was established by PLS (R2, 0.9787; RMSEC, 5.51). The developed method was applicable for rapid (c.a. 5min) and quantitative analysis of formaldehyde in squids with LOD of 15mg/kg.

Three new aaptamine derivatives from the South China Sea sponge Aaptos aaptos.

Three new aaptamine derivatives (1-3), together with six known related compounds (4-9), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Compounds 1, 4, 5, 7, and 9 showed cytotoxic activities against HeLa, K562, MCF-7, and U937 cell lines with IC50 values in the range of 0.90-12.32 µM.

Cytotoxic Bryostatin Derivatives from the South China Sea Bryozoan Bugula neritina.

Four new macrocyclic lactones, bryostatin 21 (1) and 9-O-methylbryostatins 4, 16, and 17 (2-4), together with three known related compounds, bryostatins 4, 16, and 17 (5-7), have been isolated from an extract of the South China Sea bryozoan Bugula neritina. The structures of all compounds were unambiguously elucidated using detailed spectroscopic analysis. Structurally, the presence of a single methyl group at C-18 in compound 1 has not been observed before for known bryostatins. The isolated macrolides exhibited inhibitory effects against a small panel of human cancer cell lines.

Aaptamine derivatives with antifungal and anti-HIV-1 activities from the South China Sea sponge Aaptos aaptos.

Five new alkaloids of aaptamine family, compounds (1-5) and three known derivatives (6-8), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated by spectroscopic analyses, as well as by comparison with the literature data. Compounds 1-2 are characterized with triazapyrene lactam skeleton, whereas compounds 4-5 share an imidazole-fused aaptamine moiety. These compounds were evaluated in antifungal and anti-HIV-1 assays. Compounds 3, 7, and 8 showed antifungal activity against six fungi, with MIC values in the range of 4 to 64 µg/mL. Compounds 7-8 exhibited anti-HIV-1 activity, with inhibitory rates of 88.0% and 72.3%, respectively, at a concentration of 10 µM.

Cytotoxic aaptamine derivatives from the South China Sea sponge Aaptos aaptos.

Nine new aaptamine derivatives (1-9), together with three known related compounds (10-12), have been isolated from the South China Sea sponge Aaptos aaptos. The structures of all compounds were unambiguously elucidated on the basis of spectroscopic analyses. Structurally, compound 1 possesses a piperidinyl group fused to a demethyl(oxy)aaptamine moiety, whereas compounds 3-6 share an imidazole-fused 1H-benzo[de][1,6]naphthyridin-2(4H)-one skeleton. The cytotoxic activities of the compounds were evaluated against various human cancer cell lines, and compounds 2, 8, 11, and 12 showed potent cytotoxicities against HL60, K562, MCF-7, KB, HepG2, and HT-29 cells, with IC50 values in the range of 0.03 to 8.5 µM.

Scalarane sesterterpenes from the Paracel Islands marine sponge Hyrtios sp.

A new scalarane sesterterpene, sesterstamide (1), together with four known sesterterpenes (2-5), were isolated from the Paracel Islands marine sponge Hyrtios sp. The chemical structures were established on the basis of spectroscopic analysis and comparison with known compounds. The cytotoxic and antileishmanial activities of the isolated compounds were also evaluated.

N-containing metabolites from the marine sponge Agelas clathrodes.

A new bisuracil analogue, 3,3-bis(uracil-1-yl)-propan-1-aminium (1), together with four known N-containing metabolites (2-5), were isolated from the South China Sea sponge Agelas clathrodes. Their chemical structures were established on the basis of spectroscopic and spectrometric analysis and comparison with known compounds. Compound 1 is an unusual naturally occurring bisuracil analogue, and compound 2 was isolated from a natural source for the first time. Compounds 2 and 4 exhibit moderate cytotoxicity against cancer cell line SGC7901.

Woodylides A-C, new cytotoxic linear polyketides from the South China Sea sponge Plakortis simplex.

Three new polyketides, woodylides A-C (1-3), were isolated from the ethanol extract of the South China Sea sponge Plakortis simplex. The structures were elucidated by spectroscopic data (IR, 1D and 2D NMR, and HRESIMS). The absolute configurations at C-3 of 1 and 3 were determined by the modified Mosher's method. Antifungal, cytotoxic, and PTP1B inhibitory activities of these polyketides were evaluated. Compounds 1 and 3 showed antifungal activity against fungi Cryptococcus neoformans with IC50 values of 3.67 and 10.85 µg/mL, respectively. In the cytotoxicity test, compound 1 exhibited a moderate effect against the HeLa cell line with an IC50 value of 11.2 µg/mL, and compound 3 showed cytotoxic activity against the HCT-116 human colon tumor cell line and PTP1B inhibitory activity with IC50 values of 9.4 and 4.7 µg/mL, respectively.