Design, synthesis and antitumor activity study of PARP-1/HDAC dual targeting inhibitors.

Both poly(ADP-ribose)polymerase-1 (PARP-1) and histone deacetylase (HDAC) are important antitumor targets and have attracted extensive attention. In this work, a total of fourteen PARP-1/HDAC dual targeting inhibitors were designed and synthesized using either benzopyrazole or benzimidazole as core structures. Two leading compounds 1-8-6 and 1-8-7 were proven to be dual targeting inhibitors of PARP-1 and HDAC6, and showed high antiproliferative activities against six human cancer cell lines with IC50 values in micromole range. Moreover, compounds 1-8-6 and 1-8-7 could impair tumor cell proliferation in 48 h and 72 h with much higher potency than co-treatment of Olaparib and Tubastatin A. 1-8-6 displayed remarkable anti-migration and anti-angiogenesis activities. Meanwhile, western blot experiment result showed that 1-8-6 was able to heighten expression level of acetylated α-tubulin with marginal effects to acetylated histones H3 and H4. Finally, docking simulation work showed that 1-8-6 could fit into the active sites of PARP-1 and HDAC6. All results indicated that 1-8-6 is a promising candidate for further preclinical studies.

Design, synthesis and antitumor activity evaluation of novel HDAC inhibitors with tetrahydrobenzothiazole as the skeleton.

HDACs as important targets for cancer therapy have attracted extensive attentions. In this work, a series of sixteen hydroxamic acid based HDAC inhibitors were designed and synthesized with 4,5,6,7-tetrahydrobenzothiazole as the structural core. Majority of them exhibited potent inhibitory activities against HDACs and one leading compound 6h was dug out. 6h was proven to be a pan-HDAC inhibitor and displayed high cytotoxicity against seven human cancer cell lines with IC50 values in low micromolar range. 6h could arrest cell cycle in G2/M phase and induce apoptosis in A549 cells. Moreover, compound 6h exhibited remarkable anti-migration and anti-angiogenesis activities. At the same time, 6h was able to elevate the expression of acetylated α-tubulin and acetylated histone H3 in a dose-dependent manner. Docking simulation revealed that 6h fitted well into the active sites of HDAC2 and 6. Finally, compound 6h also exerted potent antitumor effects in an A549 zebrafish xenograft model. Our study demonstrated that compound 6h was a promising candidate for further preclinical studies.

Preparation of single-crystal ternary cathode materials via recycling spent cathodes for high performance lithium-ion batteries.

With the rapid consumption of lithium-ion batteries (LIBs), the recycling of spent LIBs is becoming imperative. However, the development of effective and environmentally friendly methods towards the recycling of spent LIBs, especially waste electrode materials, still remains a great challenge. Herein, on the basis of a Li-based molten salt, we have developed a facile and effective strategy to recycle spent polycrystalline ternary cathode materials into single-crystal cathodes. The regenerated plate-like single-crystal LiNi0.6Co0.2Mn0.2O2 material with exposed {010} planes achieves an excellent rate performance and outstanding cycling stability. In particular, a high capacity of 155.1 mA h g-1 and a superior capacity retention of 94.3% can be achieved by the recycled cathode material even after 240 cycles at 1 C. Meanwhile the single-crystal structure can be well reserved without any cracks or pulverization being observed. Moreover, this recycling method can be expanded to recycle other waste Ni-Co-Mn ternary cathode materials (NCM) or their mixtures for producing high-performance single-crystal cathode materials, demonstrating its versatility and flexibility in practical applications. Therefore, the strategy of converting spent NCM cathodes into single-crystal ones with satisfactory electrochemical performance may open up a cost-effective pathway for resolving the issues caused by the large amounts of spent LIBs, thus facilitating the sustainable development of LIBs.