The synthesis and bioactivities of ROCK2 inhibitors with 1,2-dithiolan-3-yl motif.

Rho-associated coiled-coil containing kinase (ROCK) plays an important role in inflammation. Herein, a series of compounds were designed and synthesized as ROCK inhibitors based on the structure-based drug design (SBDD) strategy and were evaluated for cytotoxicity, antioxidant activity and anti-inflammatory activity. Among them, compound DC24 was identified as the optimal hit in enzymatic screening with an IC value of 0.

Synthesis and evaluation of L-quebrachitol derivatives against platelet aggregation.

Thrombosis plays an important role in the occurrence and development of cardiovascular and cerebrovascular diseases that contribute to high mortality and morbidity in patients. L-(-)-Quebrachitol (QCT), a natural product, was first isolated from quebracho bark. It can inhibit PAF receptor and decrease gastric damage induced by indomethacin, as a drug against platelet aggregation.

DNA Methyltransferase 3A: A Significant Target for the Discovery of Inhibitors as Potent Anticancer Drugs.

DNA methyltransferase (DNMT) is a conserved family of Cytosine methylases, which plays a crucial role in the regulation of Epigenetics. They have been considered promising therapeutic targets for cancer. Among the DNMT family, mutations in the DNMT3A subtype are particularly important in hematologic malignancies.

Toll-like receptor 4 (TLR4) inhibitors: Current research and prospective.

Toll-like receptor 4 (TLR4), a member of the Toll-like receptor (TLR) family, is involved in innate immunity and mediates inflammatory responses by recognizing lipopolysaccharide (LPS) or bacterial endotoxins. Hyperactivation of TLR4 triggers the production of various inflammatory factors, which are associated with the development of a variety of diseases, such as sepsis, endotoxemia, acute lung injury, rheumatoid arthritis, and cardiovascular diseases. And anti-inflammatory potential of TLR4 inhibitors have been validated.

OAB-14 Effectively Ameliorates the Dysfunction of the Endosomal-Autophagic-Lysosomal Pathway in APP/PS1 Transgenic Mice.

In Alzheimer's disease (AD), damaged Aβ clearance contributes to elevated levels of Aβ that cause a series of cytotoxic cascade reactions. Thus, targeting Aβ clearance has now been considered a valid therapeutic approach for AD. Cellular uptake and degradation are important mechanisms for Aβ clearance, which are mainly performed by the endosomal-autophagic-lysosomal (EAL) pathway.

Discovery of memantyl urea derivatives as potent soluble epoxide hydrolase inhibitors against lipopolysaccharide-induced sepsis.

Sepsis, a systemic inflammatory response, caused by pathogenic factors including microorganisms, has high mortality and limited therapeutic approaches. Herein, a new soluble epoxide hydrolase (sEH) inhibitor series comprising a phenyl ring connected to a memantyl moiety via a urea or amide linkage has been designed. A preferential urea pharmacophore that improved the binding properties of the compounds was identified for those series via biochemical assay in vitro and in vivo studies.

SET Protein in Cancer: A Potential Therapeutic Target.

SET protein is a multi-functional oncoprotein that is ubiquitously expressed in most tumor cells. Dysregulation of SET has been associated with many types of cancer. Due to ever-accumulating evidence of its strong correlation with both poor prognosis and drug resistance, the targeting of SET is starting to be explored.

Targeting HDAC/OAZ1 axis with a novel inhibitor effectively reverses cisplatin resistance in non-small cell lung cancer.

Cisplatin yields significant efficacy and is generally used as a frontline therapy for non-small cell lung cancer (NSCLC). However, acquired resistance strongly limits its application. Here, we identified that a novel histone deacetylase (HDAC) inhibitor S11, with P-glycoprotein inhibitory activity, could obviously suppress cell growth in cisplatin-resistant NSCLC cell lines.

Design, synthesis and evaluation of N-hydroxypropenamides based on adamantane to overcome resistance in NSCLC.

A series of novel N-hydroxypropenamides containing adamantane moiety were identified and most of them exhibited HDAC inhibitory activity and could reverse the resistance of cisplatin in NSCLC cell lines. In this process, molecular docking was employed to verify the rationality of designing, subsequently, target compounds were synthesized and conducted to enzyme- and cell-based biological evaluation. Most of synthesized compounds could inhibit HDAC activity with the IC values lower than 50 nM and result in the increase of Ac-H4 and p21 in A549 cells.

Insight into the roles of tightly and loosely bound extracellular polymeric substances on a granular sludge in ammonium nitrogen removal.

To explicitly understand the function of extracellular polymeric substances in the treatment of ammonium-nitrogen-rich wastewater using aerobic granular sludge, the three forms of nitrogen (ammonium, nitrite and nitrate nitrogen) contained in tightly and loosely bound extracellular polymeric substances were analyzed. The three forms of nitrogen were monitored in the tightly and loosely bound extracellular polymeric substances in aerobic granular sludge after adsorption. The ammonium nitrogen contained in the extracellular polymeric substances was distributed in both the tightly and loosely bound forms and decreased gradually as the aeration time increased.

SYP-5, a novel HIF-1 inhibitor, suppresses tumor cells invasion and angiogenesis.

Hypoxia-inducible factor-1 (HIF-1) plays an essential role in carcinogenesis. The overexpression of HIF-1 induced by hypoxia is closely associated with metastasis, poor prognosis and high mortality. In this study, a novel HIF-1 inhibitor SYP-5 was first observed by the luciferase reporter assay.

Novel cinnamohydroxamic acid derivatives as HDAC inhibitors with anticancer activity in vitro and in vivo.

A novel series of cinnamohydroxamic acid derivatives were synthesized and their biological activities against HDAC were assessed. Our results showed that the compound with more strong inhibitory activity to HDAC would exhibited more significant anti-proliferative effect on tumor cells. Among these compounds, 7e displayed clearly inhibitory effects on HDAC and tumor cell growth.