摘要：We develop here a simple wet chemistry to prepare covalent functionalized graphenes （FGs） through epoxide aminolysis espe- cially under alkaline aqueous condition. Remarkably, a series of typical monoamines, such as industrial Huntsman Jeffamine M-2070 and M-2005 polymer with hydrophilic or hydrophobic polyetheramine chains, positively-charged 2-amino-N,N,N- trimethylpropanaminium, negatively-charged sulfanilic acid, even oligopeptide sequence, can be effectively grafted on the platelets of graphene oxide precursor with covalent functionalization and partially reduced features. This strategy provides the researchers a facile and convenient approach to design and synthesize solution processable, biocompatible and functionalized graphenes for the potent applications in electronic inks, drug carriers and biomedicines. Expansion of the current study is actively ongoing in our laboratory.

摘要：A series of hydrazine and oxadiazole analogs of Sorafenib was designed, synthesized and characterized by proton nuclear magnetic resonance（1H NMR） spectrometry and high resolution mass spectrometry（HRMS）. The anti-proliferative activities of these compounds against human colorectal earcinoma（HCT-116） and human breast cancer （MDA-MB-231） tumor cell lines were evaluated in vitro by MTT method[MTT=3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide]. The bioassay results suggest that most of the synthesized compounds have antitumor potential to HCT-116 cell line compared with MDA-MB-231 cell line. Compounds 8a, 8b, 8d, Be, 9f and 9j competitive with Sorafenib demonstrated antiproliferative activities on HCT-116 cell line.

摘要：Scavenging reactive oxygen species(ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury(CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H2 O2-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 couldemerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment.

摘要：In this study,we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo *** assays indicated that most of the compounds significantly inhibited multiple cancer cells *** addition,all the compounds displayed Topo Ⅱ inhibition activity at 10 mol/L,and also possessed good PARP-1 inhibitory *** mechanistic studies showed that compound 9 a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 *** study suggested that 9 a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.

摘要：Cisplatin is one of the most successful antitumor agents, yet also restricted by its poor cellular uptake and low selectivity. Since 3-(2-nitrophenyl) propionic acid(NPPA) has been reported as a bioreductive prodrug moiety, herein we combined NPPA with cisplatin(compound 1) to improve its lipophilicity and targetability and then to improve the antitumor outcomes. In addition, compound 2 possessing 3-phenyl propionic acid(PPA) was also synthesized as a comparison to test the influence of the NPPA to the cytotoxicity, since PPA was not a bioreductive moiety. Bioevaluations showed that 1 displayed more potent antitumor potency than cisplatin and 2, suggesting Pt(II) complexes possessing NPPA groups may be a good strategy for future platinum drug discovery.

摘要：Three series of novel anti-immunodeficiency virus 1 （HIV-1） dual （RT/1N） inhibitors were rationally designed by introducing a functioning diketo acid （DKA） into pyridin-2-one scaffold. To efficiently analyze inhibitory activity, these compounds were screened against HIV-1 RT and IN respectively via surface plasmon resonance （SPR）, and active compounds were subsequently evaluated by enzyme assay. It was noteworthy that compound A2 exhibited moderate activity against both HIV-1 RT and IN. This result provided information for further development of pyridinone analogues as potent dual HIV-1 inhibitors.

摘要：In the present study,novel ester derivatives of CAPE were designed and synthesized as neuroprotective *** anti-inflammatory and antioxidant activities of these compounds were evaluated at the cellular level,while the blood-brain barrier(BBB)permeability was predicted by parallel artificial membrane permeability assay(PAMPA).The results revealed that phenolic hydroxyl groups and double bonds in the structure of CAPE had important effects on neuroprotective ***,a preliminary structure-activity relationship was summarized in this *** addition,we observed a significant improvement on BBB *** results provided important references for the structural modification and optimization of CAPE in the future.

摘要：The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differenti- ation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen （BS）, a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD^4-CD8^＋ T lymphocytes and the secretion of downstream cytokines in mice via downregulating the expression of programmed death-ligand 1 （PD-L1） on the tumor cells＇ surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 （STAT3） phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.

摘要：With rapid spread of HIV(human immunodeficiency virus) on a global scale and increasingly severe drug-resistance of it,it is urgently necessary to develop novel effective anti-HIV ***-nucleoside reverse transcriptase inhibitor(NNRTIs)is one of the most significant antiretroviral drugs for fighting against HIV infection due to their various structures,unique mode of action,good efficacy and low *** derivatives,a type of NNRTIs,have been reported to achieve remarkable development in the past few *** this review,we summarized current drug design and medicinal chemistry efforts toward the development of next-generation pyridinones as HIV-1 NNRTIs.

摘要：A series of α,β-unsaturated ketone derivatives were synthesized, and their anti-inflammatory activity toward NLRP3 inflammasome was evaluated in vitro. Several compounds were identified as anti-inflammatory agents, among which compound A21 exhibited potent anti-inflammatory activity in a dose-dependent manner with an IC50）of 0.95 μM. Moreover, a preliminary structure-activity relationship was also summarized.