Synthesis, biological evaluation and molecular docking studies of novel diosgenin derivatives as anti-inflammatory agents.

Thirty-two novel DG F-spiroacetal ring-opening derivatives, including 24 acetylated derivatives and 8 nitrogenous derivatives, were designed and synthesized from diosgenin (DG). The cytotoxicity of the novel derivatives was evaluated by MTT assay, except for compounds 4a, 4e, 4i, 4 l, 5a and 5 h, which were potentially cytotoxic to RAW264.7 cells, all the other derivatives had no significant cytotoxicity. The NO release inhibitory activities of novel derivatives were screened by Griess method. The results showed that the anti-inflammatory activity of the DG acetylated derivatives was stronger than the nitrogenous derivatives, and 4a-4 m containing acetyl groups at the 3-position may have better anti-inflammatory effects than 5a-5 k containing free hydroxyl groups. In ELISA assay, compound 4 m exhibited potent anti-inflammatory activity by inhibiting the production of NO in RAW264.7 cells activated by LPS with IC50 values 0.449 ± 0.050 µM. The results of docking experiments showed that 4 m has a good affinity for p65 protein.

Design, synthesis, and biological evaluation of stapled ascaphin-8 peptides.

Ascaphin-8 is an α-helical anti-tumor and antimicrobial peptide containing 19 residues, which was isolated from norepinephrine-stimulated skin secretions of the North American tailed frog Ascaphus truei. To improve both its stability and biological activities, a series of hydrocarbon-stapled analogs of Ascaphin-8 were synthesized and investigated for their potential antiproliferative activities. The activity studies were evaluated using the CCK-8 method and colony formation assay on human cancer cell lines. Ascaphin-8-3, as the most active peptide, showed a stronger inhibition effect when compared with the parent peptide for the tested cell lines. In addition, the effect of Ascaphin-8-3 on inhibiting the metastatic capabilities of A549 cells was more powerful than that of the parent peptide. This peptide derivative showed potentiality for further optimization in antitumor drugs.

Synthesis and Antibacterial Evaluation of a Series of 11,12-Cyclic Carbonate Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives.

A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against seven kinds of susceptible strains. In particular, compound G1 exhibited the most potent activity against methicillin-resistant Streptococcus pneumoniae 943 (MIC: 1 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), Streptococcus pyogenes 447 (MIC: 8 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, four-, four-, four-, and eight-fold stronger activity than azithromycin, respectively. Additionally, compound G2 exhibited improved activity against methicillin-resistant Staphylococcus aureus MRSA-1 (MIC: 8 µg/mL), Streptococcus pneumoniae 943 (MIC: 2 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, two-, four-, and eight-fold better activity than azithromycin, respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound G6 presented the most excellent activity (MIC: 4 µg/mL), showing four-fold higher activity than azithromycin (MIC: 16 µg/mL) and erythromycin (MIC: 16 µg/mL). However, compared with other compounds, compounds G7 and G8 with the disaccharide side chain were observed the lower activity against seven strains.

Patient and clinician perspectives on shared decision-making in infertility treatment: A qualitative study.

OBJECTIVES: To explore the considerations and barriers to implementing shared decision-making (SDM) in infertility treatment among female infertility patients, their male spouses, and fertility clinicians. METHODS: Participants were recruited from a reproductive medicine hospital in China's Shandong Province using purposive sampling. One-on-one interviews were held with female infertility patients and their spouses. In addition, a focus group discussion was conducted with fertility clinicians. Data analysis was subjected to open, axial, and selective coding. RESULTS: Nineteen female infertility patients and 10 male spouses were interviewed one-on-one. Five clinicians participated in the focus group discussion. Most female patients wanted to participate in the decision-making process, and that spouses and fertility clinicians supported SDM. Furthermore, key barriers were identified from the perspectives of multiple stakeholders, including communication difficulties, psychological pressure on female patients, patient preferences, multiple treatment stages, male spousal participation, clinician-patient trust, and subjective patient factors. CONCLUSIONS/PRACTICE IMPLICATIONS: This study explored the considerations of and barriers to implementing SDM in infertility treatment. Key barriers were identified from the perspectives of multiple stakeholders. Based on the findings, clinicians should encourage patients and their spouses to actively participate in decision-making, and provide objective and realistic guidance.