Design, synthesis, and antitumor activity of PLGA nanoparticles incorporating a discovered benzimidazole derivative as EZH2 inhibitor

Synthesis of imidazo[4,5-e][1,3]thiazino[2,3-c][1,2,4]triazines via a base-induced rearrangement of functionalized imidazo[4,5-e]thiazolo[2,3-c][1,2,4]triazines

“…Nitrogen- and sulfur-containing heterocyclic compounds are widely represented in nature and used for the synthesis of biologically active substances. Among the 1,3-thiazine derivatives, promising compounds as antimicrobial and antiviral drugs (PD404182) [ 1 – 4 ], sedative [ 5 ] and antitumor agents [ 6 – 8 ], as well as fungicides [ 9 – 10 ] and insecticides [ 11 ] have been found ( Figure 1 ). The 1,3-thiazine heterocyclic system is comprised in some natural phytoalexins (cyclobrassinin, sinalbins A and B, rutalexin, and others) [ 12 ] and 7-aminocephalosporanic acid (7-ACA), which is a key fragment of broad-spectrum cephalosporin antibiotics [ 13 – 14 ].…”

Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure–Activity Relationships Insights and Evolution Prospects

“…Polymer nanoparticles can penetrate biological barriers, promote passive targeting of chemotherapeutic drugs to tumor cells, enhance antitumor activity, prolong circulation time, and significantly reduce drug side effects . Poly­( d , l -lactide- co -glycolide) (PLGA) material is a common nanodrug carrier with excellent biocompatibility and biodegradability. , Elkot et al improved the activity of compounds by introducing a benzimidazole structure, and combining PLGA nanoparticles with an active drug can improve their PK and pharmacodynamic properties . SAR studies showed that the introduction of a methoxy group on the benzene ring ( 141a ) enhanced its antitumor activity, and the inhibitory rates on HepG-2, MCF-7, and PC-3 cells were 64%, 50.8%, and 36.7%, respectively.…”

“…147,148 Elkot et al improved the activity of compounds by introducing a benzimidazole structure, and combining PLGA nanoparticles with an active drug can improve their PK and pharmacodynamic properties. 149 SAR studies showed that the introduction of a methoxy group on the benzene ring (141a) enhanced its antitumor activity, and the inhibitory rates on HepG-2, MCF-7, and PC-3 cells were 64%, 50.8%, and 36.7%, respectively. The introduction of methyl and chlorine atoms on benzimidazole (142a−b) reduced the activity of the compounds.…”