Moldavica acid A, a new salicylic acid derivative from .

In this paper, we present the discovery of a novel salicylic acid derivative, moldavica acid A (), and a new natural dibenzo[b,f]oxepin, moldavica acid B (), together with four known phenylpropionic acids (-) and protocatechuic acid () that were isolated from L. Their structures were elucidated by comprehensive spectroscopic methods, including infrared and nuclear magnetic resonance. Compound is the first example of salicylic acid linking a carboxylated -pyrone via an ethyl bridge.

Identification of Novel Compounds Enhancing SR-BI mRNA Stability through High-Throughput Screening.

Atherosclerosis is the pathological basis of most cardiovascular diseases. Reverse cholesterol transport (RCT) is a main mechanism of cholesterol homeostasis and involves the direct transport of high-density lipoprotein (HDL) cholesteryl ester by selective cholesterol uptake. Hepatic scavenger receptor class B member 1 (SR-BI) overexpression can effectively promote RCT and reduce atherosclerosis.

Novel cathepsin K inhibitors block osteoclasts and increase spinal bone density in zebrafish.

Cathepsin K (Cat K) is a predominant cysteine protease and highly potent collagenase expressed in osteoclasts. Cat K inhibitors are anti-resorptive agents to treat osteoporosis. A novel scaffold of cathepsin K inhibitors, exemplified by lead compound 1x, was used as the template for designing and synthesizing a total of 61 derivatives that have not been reported before.

Synthesis and Biological Evaluation of Quinoline Derivatives as a Novel Class of Broad-Spectrum Antibacterial Agents.

Nineteen new quinoline derivatives were prepared via the Mannich reaction and evaluated for their antibacterial activities against both Gram-positive (G⁺) and Gram-negative (G) bacteria, taking compound as the lead. Among the target compounds, quinolone coupled hybrid exerted the potential effect against most of the tested G⁺ and G strains with MIC values of 0.125⁻8 μg/mL, much better than those of .

T63 inhibits osteoclast differentiation through regulating MAPKs and Akt signaling pathways.

Inhibition of excessive osteoclast differentiation and activity is a valid approach for the treatment of osteoporosis. T63 is a small-molecule compound identified from a high throughput screening based on RUNX2 transcriptional activity, and has been reported to stimulate osteoblast formation. However, whether the compound has any effect on osteoclast differentiation remains unknown.

Small molecule T63 suppresses osteoporosis by modulating osteoblast differentiation via BMP and WNT signaling pathways.

Osteoporosis results from the imbalance between bone resorption and bone formation, and restoring the normal balance of bone remodeling is highly desirable for identification of better treatment. In this study, using a cell-based high-throughput screening model representing Runt-related transcription factor 2 (RUNX2) transcriptional activity, we identified a novel small-molecular-weight compound, T63, as an efficient up-regulator of osteogenesis. T63 increased the alkaline phosphatase (ALPL) activity and mineralization as well as gene expression of Alpl and other osteogenic marker genes in mouse osteoblasts and mesenchymal stem cell-like cells.

[A new benzamide derivative from rice fermentation of Streptomyces sp. CPCC 202950].

Eight compounds were isolated from the rice fermentation of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over silica, Sephadex LH-20, flash C₁₈, and reversed-phase HPLC. Their structures were identified as 3-[(3'-amino-3'-oxoprop-1'-en-2'-yl)oxy]benzamide (1), m-hydroxybenzamide (2), leptosphaepin (3), 5-methyluracil (4), feruloylamide (5), p-hydroxyphenylacetoamide (6), vanillamide (7), cyclo (L-val-L-ala) (8).

Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism.

Objective: Berberine (BBR) clinically lowers blood lipid and glucose levels via multi-target mechanisms. One of the possible mechanisms is related to its effect on the short chain fatty acids (SCFAs) of the gut microbiota. The goal of this study is to investigate the therapeutic effect and mode of action of BBR working through SCFAs of the gut microbiota (especially, butyrate).

[Screening of small molecule inhibitors for PLK1 PBD and evaluation of antitumor activities].

With the method of fluorescence polarization (FP), we screened small molecule inhibitors for PLK1 PBD to identify the lead compounds for antitumor drugs. FP led to the identification of a potent hit, F083-0063, whose inhibition rate was (99.7 ± 0.

A Novel Nitrobenzoate Microtubule Inhibitor that Overcomes Multidrug Resistance Exhibits Antitumor Activity.

Multidrug resistance is a major limitation for microtubule-binding agents in cancer treatment. Here we report a novel microtubule inhibitor (2-morpholin-4-yl-5-nitro-benzoic acid 4-methylsulfanyl-benzyl ester, IMB5046), its cytotoxicity against multidrug-resistant cell lines and its antitumor efficacy in animal models. IMB5046 disrupted microtubule structures in cells and inhibited purified tubulin polymerization in vitro.

[In vitro effect and mechanistic study of compound E23869 on lipid metabolism].

This study was designed to identify inducers of ATP-binding cassette transporter A1(ABCA1) and CD36 and lysosomal integral membrane protein-II analogous-1(CLA-1) and to evaluate the in vitro effect of the active compound on lipid metabolism. Among 20 000 compounds screened, E23869 was found as a positive hit using cell-based high throughput screening models. The up-regulating activities of E23869 in ABCA1p-LUC and CLA-1p-LUC Hep G2 cells were 196% and 198%, respectively.

[Evaluation of osteogenic effects of BMP2 up-regulator E40071 in vitro].

Bone morphogenetic protein 2(BMP2) plays a key role in bone development and reestablishment. In the study, we screened up-regulators of BMP2 among 20 000 compounds through a cell-based high throughput screening model and a positive compound E40071 [2-(4-(5-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-7-yl) piperazin-1-yl)ethan-1-ol] was found as the positive hit. The EC(50) value of E40071 was 2.

[A novel trichostatin analogue culture of Streptomyces sp. CPCC 203909].

By using a cell-based high throughput screening model for the CLA-1 up-regulator, Streptomyces 203909 was found to produce up-regulator of CLA-1. A novel trichostatin analogue was isolated from the rice fermentation of Streptomyces sp. CPCC 203909by a combination of various chromatographic techniques including column chromatography (CC) over silica gel, flash C18 CC, and reversed-phase HPLC.

[Chemical constituents from culture of Streptomyces sp. CPCC 202950].

Eleven compounds were isolated from the culture of Streptomyces sp. CPCC 202950 by a combination of various chromatographic techniques including column chromatography over macroporous resin HP-20, MCI, and reversed-phase HPLC. Their structures were identified as 1H-pyrrole-2-carboxamide(1),5'-deoxy-5'-methylthioinosine(2), vanillamide(3), trans-3-methylthioacrylamide(4), 1,2,3,4-Tetraydro-1H-pyrido[3,4-b]indole-3-carboxylic acid(5), cyclo(L-pro-L-tyr) (6), N-[2-(4-hydroxyphenyl)]ethylacetamide(7), benzamide (8), cyclo ('L-leucyl-trans-4-hydroxy-L-proline)(9), cyclo-(Phe-Gly) (10), and tryptophan (11).

A new trichostatin analog from Streptomyces sp. CPCC 203909.

A new trichostatin analog (1) and two known analogs (2, 3) have been isolated from the rice fermentation of the Streptomyces sp. CPCC 203909. Their structures were determined by spectroscopic and chemical methods.