Fabrication of Biodegradable and Biocompatible Functional Polymers for Anti-Infection and Augmenting Wound Repair.

The problem of bacteria-induced infections threatens the lives of many patients. Meanwhile, the misuse of antibiotics has led to a significant increase in bacterial resistance. There are two main ways to alleviate the issue: one is to introduce antimicrobial agents to medical devices to get local drug releasing and alleviating systemic toxicity and resistance, and the other is to develop new antimicrobial methods to kill bacteria.

Nonpeptidic quinazolinone derivatives as dual nucleotide-binding oligomerization domain-like receptor 1/2 antagonists for adjuvant cancer chemotherapy.

Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.

Identification of benzofused five-membered sultams, potent dual NOD1/NOD2 antagonists in vitro and in vivo.

Nucleotide-binding oligomerization domain-containing proteins 1 and 2 play important roles in immune system activation. Recently, a shift has occurred due to the emerging knowledge that preventing nucleotide-binding oligomerization domains (NODs) signaling could facilitate the treatment of some cancers, which warrants the search for dual antagonists of NOD1 and NOD2. Herein, we undertook the synthesis and identification of a new class of derivatives of dual NOD1/NOD2 antagonists with novel benzofused five-membered sultams.

Discovery of (1-Pyrazolo[3,4-]pyridin-5-yl)sulfonamide Analogues as Hepatitis B Virus Capsid Assembly Modulators by Conformation Constraint.

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) have been suggested to be effective anti-HBV agents in both preclinical and clinical studies. In addition to blocking HBV replication, CAMs could reduce the formation of covalently closed circular DNA (cccDNA), which accounts for the persistence of HBV infection. Here, we describe the discovery of (1-indazole-5-yl)sulfonamides and (1-pyrazolo[3,4-]pyridin-5-yl)sulfonamides as new CAM chemotypes by constraining the conformation of the sulfamoylbenzamide derivatives.

Discovery of Potent Inhibitors against P-Glycoprotein-Mediated Multidrug Resistance Aided by Late-Stage Functionalization of a 2-(4-(Pyridin-2-yl)phenoxy)pyridine Analogue.

SIS3 is a specific inhibitor of Smad3 that inhibits the TGFβ1-induced phosphorylation of Smad3. In this article, a variety of SIS3 derivatives were designed and synthesized to discover potential inhibitors against P-glycoprotein-mediated multidrug resistance aided by late-stage functionalization of a 2-(4-(pyridin-2-yl)phenoxy)pyridine analogue. A novel class of potent P-gp reversal agents were investigated, and a lead compound was identified as a potent P-gp reversal agent with strong bioactivity and outstanding affinity for P-gp.

Discovery of New Hepatitis B Virus Capsid Assembly Modulators by an Optimal High-Throughput Cell-Based Assay.

In this article, a simple and effective high-throughput screening (HTS) assay was developed to identify anti-HBV compounds by using a HepAD38 luciferase reporter (HepAD38-luc) cell line that can effectively exclude the false positive hit compounds targeted on the tetracycline off (tet-off) regulation system. Through screening in-house chemical libraries, N-phenylpiperidine-3-carboxamide derivatives, represented by 1 and 2, were identified, while the other false positive hits (i.e.

Past, Current, and Future Developments of Therapeutic Agents for Treatment of Chronic Hepatitis B Virus Infection.

For decades, treatment of hepatitis B virus (HBV) infection has been relying on interferon (IFN)-based therapies and nucleoside/nucleotide analogues (NAs) that selectively target the viral polymerase reverse transcriptase (RT) domain and thereby disrupt HBV viral DNA synthesis. We have summarized here the key steps in the HBV viral life cycle, which could potentially be targeted by novel anti-HBV therapeutics. A wide range of next-generation direct antiviral agents (DAAs) with distinct mechanisms of actions are discussed, including entry inhibitors, transcription inhibitors, nucleoside/nucleotide analogues, inhibitors of viral ribonuclease H (RNase H), modulators of viral capsid assembly, inhibitors of HBV surface antigen (HBsAg) secretion, RNA interference (RNAi) gene silencers, antisense oligonucleotides (ASOs), and natural products.