摘要：A series of novel pyrazole-based lipoprotein-associated phospholipase A2 （Lp-PLA2） inhibitors have been de- signed and synthetized by a variety of acetophenones via a 10-step convergent approach. The synthetic approach is carefully optimized, and an unsuccessful alternative route is also discussed. The in vitro biological activity reveals that all the synthesized compounds are potent Lp-PLA2 inhibitors with compound 13b being the most potent one （Lp-PLA2, IC50= 1.5 nmol/L）.

摘要：Dipeptidyl peptidase 4(DPP-4)is a clinically validated target for the treatment of type 2 diabetes mellitus(T2DM).To discover novel and potent DPP-4 inhibitors,three series of compounds were designed and synthesized in this study based on our previously identified novel scaffold of 2-phenyl-3,4-dihydro-2H-benzo[f]*** the designed compounds,41d-1 was the most po tent one with an IC_(50) value of 16.00 nM.

摘要：Objective:To find potential peptide inhibitors against the NS2B/NS3 protease of DENV which in turn,can inhibit the viral replication inside host ***:Cyclic peptides were designed having combination of positively charged amino acids using ChemSketch software and were converted to 3D *** NS3 protein structure was retrieved from Protein Data Bank(PDB)using PDB Id:*** NS3 and cylic peptides were docked using MOE software after structural ***:Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had interactions with catalytic *** 2 successfully blocked the catalytic triad of NS2B/NS3 *** 1,,4 and 6 also had potential interactions with active residues of the NS2B/NS3 protease while all other peptides were in close contact with the active sites of NS2B/NS3 protease thus,these peptides can serve as a potential drug candidate to stop viral ***:*** can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.

摘要：The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX 106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX 106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX 106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX 106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the Pglycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX 106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.

摘要：Human rhinoviruses(HRVs)are the predominant infectious agents for the common cold *** HRV-C species cause severe illnesses in children and are closely related to acute exacerbations of asthma.3C protease,a highly conserved enzyme,cleaves the viral polyprotein during replication and assists the virus in escaping the host immune *** key roles make 3C protease an important drug target.A few structures of 3Cs complexed with an irreversible inhibitor rupintrivir have been *** structures shed light on the determinants of drug *** we describe the structures of HRV-C153C in free and inhibitor-bound *** volume-decreased S1'subsite and half-closed S2 subsite,which were thought to be unique features of enterovirus A 3C proteases,appear in the HRV-C 3C *** assumes an“intermediate”conformation in the complex,which might open up additional avenues for the design of potent antiviral *** of the features of the three-dimensional structures and the amino acid sequences of 3C proteases suggest new applications for existing drugs.

摘要：Since nucleic acids(DNA and RNA) play very important roles in cells,they are molecular targets of many clinically used drugs,such as anticancer drugs and *** of clinical demands for treating various deadly cancers and drug-resistant strains of pathogens,there are urgent needs to develop novel therapeutic *** nucleic acids hasn’t been the mainstream of drug discovery in the past,and the lack of 3D structural information for designing and developing drug specificity is one of the main ***,many important structures of nucleic acids and their protein complexes have been determined over the past decade,which provide novel platforms for future drug design and *** this review,we describe some useful nucleic acid structures,particularly their interactions with the ligands and therapeutic candidates or even *** summarize important information for designing novel potent drugs and for targeting nucleic acids and protein-nucleic acid complexes to treat cancers and overcome the drug-resistant problems.

摘要：Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.