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Bacterial wound infection has emerged as a pivotal threat to human health worldwide, and the situation has worsened owing to the gradual increase in antibiotic‐resistant bacteria caused by the improper use of antibiotics. To reduce the use of antibiotics and avoid the increase in antibiotic‐resistant bacteria, researchers are increasingly paying attention to photodynamic therapy, which uses light to produce reactive oxygen species to kill bacteria. Treating bacteria‐infected wounds by photodynamic therapy requires fixing the photosensitizer (PS) at the wound site and maintaining a certain level of wound humidity. Hydrogels are materials with a high water content and are well suited for fixing PSs at wound sites for antibacterial photodynamic therapy. Therefore, hydrogels are often loaded with PSs for treating bacteria‐infected wounds via antibacterial photodynamic therapy. In this review, we systematically summarised the antibacterial mechanisms and applications of PS‐loaded hydrogels for treating bacteria‐infected wounds via photodynamic therapy. In addition, the recent studies and the research status progresses of novel antibacterial hydrogels are discussed. Finally, the challenges and future prospects of PS‐loaded hydrogels are reviewed. [ABSTRACT FROM AUTHOR]

Background: Postoperative anastomotic leakage (PAL) is a serious complication of gastric cancer surgery. Although perioperative management has made considerable progress, anastomotic leakage (AL) cannot always be avoided. The purpose of this study is to evaluate whether intraoperative leak testing (IOLT) can reduce the incidence of PAL and other postoperative outcomes in gastric cancer surgery. Materials and methods: In this meta-analysis, we searched the PubMed, Embase, and Cochrane Library databases for clinical trials to assess the application of IOLT in gastric cancer surgery. All patients underwent laparoscopic radical gastrectomy for gastric cancer surgery. Studies comparing the postoperative outcomes of IOLT and no intraoperative leak testing (NIOLT) were included. Quality assessment, heterogeneity, risk of bias, and the level of evidence of the included studies were evaluated. PAL, anastomotic-related complications, 30-day mortality, and reoperation rates were compared between the IOLT and NIOLT group. Results: Our literature search returned 721 results, from which six trials (a total of 1,666 patients) were included in our meta-analysis. Statistical heterogeneity was low. The primary outcome was PAL. IOLT reduced the incidence of PAL [2.09% vs 6.68%; (RR = 0.31, 95% Cl 0.19–0.53, P < 0.0001]. Anastomotic-related complications, which included bleeding, leakage, and stricture, were significantly higher in the NIOLT group than in the IOLT group [3.24% VS 10.85%; RR = 0.30, 95% Cl 0.18–0.53, P < 0.0001]. Moreover, IOLT was associated with lower reoperation rates [0.94% vs 6.83%; RR = 0.18, 95% CI 0.07–0.43, P = 0.0002]. Conclusion: Considering the observed lower incidence of postoperative anastomotic leakage (PAL), anastomotic-related complications, and reoperation rates, IOLT appears to be a promising option for gastric cancer surgery. It warrants further study before potential inclusion in future clinical guidelines. [ABSTRACT FROM AUTHOR]

Both isoindolinones and continuous quaternary carbons play important roles in pharmaceutical scaffolds. However, few examples have been developed to construct isoindolinones containing continuous quaternary carbons due to the steric hindrance effect. Here, a rhodium(II)-catalyzed reaction of 3-hydroxyisoindolinones and diazos via an intermolecular OH transfer to deliver the isoindolinone derivatives containing continuous quaternary carbons as products is developed in high yields of up to 89% via an intermolecular OH transfer with a green chemistry metric E-factor of 5.70. The resulting products exhibit antiviral activity against SARS-CoV-2 3CL protease (3CLpro) and control investigations show that the quaternary carbons and hydroxyl group are essential for the bioactivity. [ABSTRACT FROM AUTHOR]

A Rh(II)/boron reagent co-catalyzed unprecedent transformation was established for the rapid construction of multi-substituted conjugated dienones under mild conditions by trapping allene carbocations with oxonium ylides from simple starting points in yields up to 85%. Two C＝C double bonds, one C–C and one C–O single bond were built in this one-pot reaction. The diversity-oriented strategy was also established to synthesize alkyne ether and dihydrofuran derivatives by a substrate-depended fashion. [ABSTRACT FROM AUTHOR]

Chemotherapy combining with surgical treatment has been the main strategy for osteosarcoma treatment in clinical. Due to unclear pathogenesis and unidentified drug targets, significant progress has not been made in the development of targeted drugs for osteosarcoma during the past 50 years. Our previous discovery reported compound R - 8i with a high potency for the treatment of osteosarcoma by phenotypic screening. However, both the metabolic stability and bioavailability of R - 8i are poor (T 1/2 = 5.36 min, mouse liver microsome; and bioavailability in vivo F = 52.1 %, intraperitoneal administration) which limits it use for further drug development. Here, we described an extensive structure−activity relationship study of thiazolidine-4-one sulfone inhibitors from R - 8i , which led to the discovery of compound 68. Compound 68 had a potent cellular activity with an IC 50 value of 0.217 μM, much higher half-life (T 1/2 = 73.8 min, mouse liver microsome) and an excellent pharmacokinetic profile (in vivo bioavailability F = 115 %, intraperitoneal administration). Compound 68 also showed good antitumor effects and low toxicity in a xenograft model (44.6 % inhibition osteosarcoma growth in BALB/c mice). These results suggest that compound 68 is a potential drug candidate for the treatment of osteosarcoma. [Display omitted] • Discovering lead compound 68 from the metabolites for anti-osteosarcoma. • 68 shows an obviously improved metabolic stability with 115 % bioavailability in vivo. • Compound 68 possesses 44.6 % inhibition osteosarcoma growth and low toxicity in mice. • Compound 68 significantly suppresses osteosarcoma cell migration in vitro. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to human. Since there are still no effective treatment options against the new emerging variants of SARS-CoV-2, it is necessary to devote a continuous endeavor for more targeted drugs and the preparation for the next pandemic. Salvia miltiorrhiza and its active ingredients possess wide antiviral activities, including against SARS-CoV-2. Danshensu, as one of the most important active ingredients in Salvia miltiorrhiza , has been reported to inhibit the entry of SARS-CoV-2 into ACE2 (angiotensin-converting enzyme 2)-overexpressed HEK-293T cells and Vero-E6 cells. However, there is a paucity of information regarding its detailed target and mechanism against SARS-CoV-2. Here, we present Danshensu as a covalent inhibitor of 3-chymotrypsin-like protease (3CLpro) against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. Further molecular docking, site-directed mutagenesis, circular dichroism (CD) and fluorescence spectra revealed that Danshensu covalently binds to C145 of SARS-CoV-2 3CLpro, meanwhile forming the hydrogen bonds with S144, H163 and E166 in the S1 site. Structure-based optimization of Danshensu led to the discovery of the promising compounds with good inhibitory activity and microsomal stability in vitro. Due to Danshensu inhibiting lung inflammation in the mouse model, we found that Danshensu derivatives also showed better anti-inflammatory activity than Danshensu in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Thus, our study provides not only the clue of the efficacy of Salvia miltiorrhiza against SARS-CoV-2, but also a detailed mechanistic insight into the covalent mode of action of Danshensu for design of covalent inhibitors against SARS-CoV-2 3CLpro, highlighting its potential as a bifunctional molecule with antivirus and anti-inflammation. • Potential target of Danshensu with anti-SARS-CoV-2 activity is discussed. • Danshensu was confirmed to covalently bind to C145 of SARS-CoV-2 3CLpro, meanwhile forming the hydrogen bonds with S144, H163 and E166 in the S1 site. • Structure-based optimization of Danshensu led to the discovery of the promising bifunctional molecules with antivirus and anti-inflammation. [ABSTRACT FROM AUTHOR]

An efficient one-pot two-step synthetic strategy to access highly selective N 2-substituted-1,2,3-triazole from aryl ethynylenes, azides and furan has been developed via a radical transformation. 17 examples of aryl ethynylene with various substituents were converted into their corresponding functionalized N 2-substituted-1,2,3-triazole derivatives in good yields. [Display omitted] [ABSTRACT FROM AUTHOR]

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)- 8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC 50 = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)- 8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)- 8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)- 8i might be a potential drug candidate for OS treatment. [Display omitted] • Thiazolidinones were discovered for treating osteosarcoma by phenotypic screening. • The screening used an in-house patrimonial collection of structural diversity. • Lead compound (R)- 8i selectively inhibit osteosarcoma cell in vitro and in vivo. • (R)- 8i also significantly suppresses osteosarcoma cell migration in vitro. • (R)- 8i presents a considerable bioavailability and a low toxicity. [ABSTRACT FROM AUTHOR]