Our team discovered a moderate SphK1 inhibitor, SAMS10 (IC50 = 9.8 μM), which was screened by computer-assisted screening. In this study, we developed a series of novel diaryl derivatives with improved antiproliferative activities by modifying the structure of the lead compound SAMS10. A total of 50 new compounds were synthesized. Among these compounds, the most potent compound, named CHJ04022Rb, has significant anticancer activity in melanoma A375 cell line (IC50 = 2.95 μM). Further underlying mechanism studies indicated that CHJ04022R exhibited inhibition effect against PI3K/NF-κB signaling pathways, inhibited the migration of A375 cells, promoted apoptosis and exerted antiproliferative effect by inducing G2/M phase arrest in A375 cells. Furthermore, acute toxicity experiment indicated CHJ04022R exhibited good safety in vivo. Additionally, it showed a dose-dependent inhibitory effect on the growth of xenograft tumor in nude mice. Therefore, CHJ04022R may be a potential candidate for the treatment of melanoma.

Purpose: To investigate and compare the analgesic effects of nerve block anesthesia and local infiltration anesthesia in one-visit root canal therapy of mandibular molars. Methods: A total of 120 patients who underwent one-visit root canal therapy for mandibular molars were divided into nerve block group (n = 76) and local infiltration group (n = 44). Lidocaine was used to anesthetize the two groups. Perioperative heart rate (HR), diastolic blood pressure (DBP) and systolic blood pressure (SBP) were determined in the two groups. Visual analogue scale (VAS) and Ramsay sedation scale were used to assess postoperative pain and sedation in the two groups. The occurrence of adverse reactions was also compared. Results: The success rate of the anesthesia in the nerve block group was significantly higher than that in local infiltration group (9 7.37 vs 88.64 %; p < 0.05). There were no significant differences in HR, DBP and SBP levels between the two groups. Over time, VAS and Ramsay scores decreased in both groups, while the VAS and Ramsay scores in the nerve block group were significantly lower than those in the local infiltration group (p < 0.05). The incidence of adverse reactions in the nerve block group was 5.26 %, which was not significantly different from 13.64 % incidence rate in local infiltration group (p > 0.05). Conclusion: Both anesthesia methods have little effect on hemodynamics in patients undergoing one-visit root canal therapy for mandibular molars, but lidocaine nerve block anesthesia is more effective and has stronger analgesic and sedative effects than lidocaine local infiltration anesthesia.