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Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives ( 8a ∼ 8e and 11a ∼ 11f ) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro . Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against SGC-7901 cell with IC 50 value 0.77 μM by inducing cell cycle arrest at G2 phase. It also could improve SGC-7901 cell apoptosis, mitochondrial membrane potential assay indicated that the dissipation of MMP might participate in apoptosis induced by title compound. In vivo studies showed that compound 8d displayed potent anticancer activity with inhibition tumor growth. [ABSTRACT FROM AUTHOR]

NLRP3 inflammasome activation plays a key role in a variety of inflammatory diseases as IBD. Here a series of pterostilbene derivatives were designed and synthesized based on previous SAR, leading to discovery of new effective NLRP3 inflammasome inhibitors with metabolic stability. Among them, the most effective compound 27 showed high inhibitory efficacy (against IL-1 β: IC 50 = 1.23 μM) and almost no toxicity (against L02: IC 50 > 100 μM). Further mechanism studies have shown that compound 27 directly targets the NLRP3 and affects the assembly of inflammasomes to inhibit the activation of NLRP3 inflammasomes. More importantly, in vitro experiments show that compound 27 has a significant therapeutic effect on DSS-induced colitis in mice with good metabolic stability to liver microsomes (t 1/2 = 138.6 min). This research encourages the further development of more effective NLRP3 inflammasome inhibitors based on this chemical scaffold. [Display omitted] • New NLRP3 inflammasome inhibitors were designed and synthesized. • The structure-based optimization and SAR study were fully carried out. • Further mechanism studies indicated it affected the assembly of inflammasomes. [ABSTRACT FROM AUTHOR]