Design, synthesis and evaluation of dihydro-1<i>H</i>-indene derivatives as novel tubulin polymerisation inhibitors with anti-angiogenic and antitumor potency

Angiogenesis plays an important role in tumour generation and progression, which is used to supply nutrients and metastasis. Herein, a series of novel dihydro-1H-indene derivatives were designed and evaluated as tubulin polymerisation inhibitors by binding to colchicine site, exhibiting anti-angiogenic activities against new vessel forming. Through structure-activity relationships study, compound 12d was found to be the most potent derivative possessing the antiproliferative activity against four cancer lines with IC50 values among 0.028−0.087 µM. Compound 12d bound to colchicine site on tubulin and inhibited tubulin polymerisation in vitro. In addition, compound 12d induced cell cycle arrest at G2/M phase, stimulated cell apoptosis, inhibited tumour metastasis and angiogenesis. Finally, the results of in vivo assay suggested that compound 12d could prevent tumour generation, inhibit tumour proliferation and angiogenesis without obvious toxicity. Collectively, all these findings suggested that compound 12d is a novel tubulin polymerisation inhibitor deserving further research.</p

Mitigating Concentration Polarization through Acid–Base Interaction Effects for Long-Cycling Lithium Metal Anodes

Lithium (Li) metal has attracted great attention as a promising high-capacity anode material for next-generation high-energy-density rechargeable batteries. Nonuniform Li+ transport and uneven Li plating/stripping behavior are two key factors that deteriorate the electrochemical performance. In this work, we propose an interphase acid–base interaction effect that could regulate Li plating/stripping behavior and stabilize the Li metal anode. ZSM-5, a class of zeolites with ordered nanochannels and abundant acid sites, was employed as a functional interface layer to facilitate Li+ transport and mitigate the cell concentration polarization. As a demonstration, a pouch cell with a high-areal-capacity LiNi0.95Co0.02Mn0.03O2 cathode (3.7 mAh cm–2) and a ZSM-5 modified thin lithium anode (50 μm) delivered impressive electrochemical performance, showing 92% capacity retention in 100 cycles (375.7 mAh). This work reveals the effect of acid–base interaction on regulating lithium plating/stripping behaviors, which could be extended to developing other high-performance alkali metal anodes