摘要：To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and *** 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination *** chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray *** 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal *** 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper ***,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric *** vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than ***,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell *** addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer ***:

摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：Main observation and conclusion A full account of the total synthesis of(-)-pallambins A-D(1-6)is *** strategy was devised by simulating their biosynthetic *** left-part bicyclo[3.2.1]octane system of pallambins C and D was efficiently constructed via a palladium-catalyzed oxidative cyclization.

摘要：Summary of main observation and conclusion Benzofuran has antifungal activity as the inhibitor of ***-nine novel benzofuran-semicarbazide hybrids were designed and synthesized by principle of drug *** this basis,the benzofuran ring was simplified to a resorcinol structure,and sixteen novel 1,3-dialkoxybenzene-semicarbazide hybrids were designed and *** structures of the target compounds were characterized by HRMS and *** in vitro antifungal activity of target compounds was evaluated using the microdilution broth method against eight strains of pathogenic fungi with fluconazole as positive *** to the results of the target compounds,structure-activity relationship(SAR)is *** inhibitory activity against the tested strains of simplified compounds(K01-K16)has different levels improvement compared with compounds Z01-Z29.K01-K16 showed significant antifungal activities against ***,***,and sensitive *** ***,compounds Z20,Z22,K10,K11 and K16 also displayed different activities against two fluconazole-resistance strains that were isolated from AIDS *** minimal inhibitory concentration(MIC)values against fluconazole-resistant strains were in the range of 2-8μg/mL and 4-32μg/mL,***,molecular docking was performed to investigate the binding affinities and interaction modes between the target compound and N-myristoyltransferase.

摘要：Novel purine-2,6-diamine derivatives were designed and synthesized as cyclin-dependent kinase （CDK） inhibi- tors. According to the preliminary biological evaluation, most of the compounds show good inhibitory activities in CDK1 enzyme assay and potent antiproliferative activities in some tumor cell lines. Especially, compound lla （IC50=0.35 μmol/L for CDK1/cyclin B and IC50： effect compared with Roscovitine （IC50= 2.54 CDK2/cyclin A）. 0.023 μmol/L for CDK2/cyclin A） possessed better inhibitory μmol/L for CDK1/cyclin B and IC50=0.092 μ mol/L for

摘要：Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis （CE） without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase （ADA）. A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly, D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-Kuanosine analogs for the treatment of HIV,

摘要：The need for long-term treatments of chronic diseases has motivated the widespread development of long-acting parenteral formulations(LAPFs)with the aim of improving drug pharmacokinetics and therapeutic *** have been proven to extend the half-life of therapeutics,as well as to improve patient adherence;consequently,this enhances the outcome of therapy *** past decades,considerable progress has been made in designing effective LAPFs in both preclinical and clinical *** we review the latest advances of LAPFs in preclinical and clinical stages,focusing on the strategies and underlying mechanisms for achieving long *** strategies are classified into manipulation of in vivo clearance and manipulation of drug release from delivery systems,*** the current challenges and prospects of each strategy are *** addition,we also briefly discuss the design principles of LAPFs and provide future perspectives of the rational design of more effective LAPFs for their further clinical translation.

摘要：A series of novel chalcone derivatives was designed and synthesized via a suitable synthetic strategy in good yields using commercially available 2-amino-4-nitrophenol as an initiator. The structures of the target compounds were confirmed by means of IH NMR, 13C NMR and high-resolution mass spectrometry（HRMS）. And the ability of the target compounds to inhibit influenza viruses was evaluated. These compounds showed moderate inhi- bitory activity against influenza A（H9N2 and H5NI） viruses. Within this series, compounds S14 and S15 with good potency（IC50=40.3--51.5 μmol/L） could be used as lead compounds in the future.

摘要：A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.

摘要：A series of novel indole derivatives were designed and synthesized and their inhibitory activity against B-Raf and HepG2 cell were also described. Among them, compounds 7a and 7b exhibited excellent potency, which showed the potential for further research as lead compounds.