A coupled transcription/translation high-throughput screening assay was miniaturized and shown to be effective at detecting known classes of ribosome-inhibiting antibiotics. This luciferase-based assay was successfully applied to a natural product extract library of 30 000 compounds with a hit-rate of 4.6%, a %CV value of 8.5% and a Z’ value of 0.74. Selected hits were retested in triplicate to confirm authenticity, subjected to a secondary screen to remove luciferase inhibitors, and are moving forward in the discovery process..

A series of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones were designed and synthesized, and their biological activities against tumor cell lines were evaluated in vitro. Compounds (E,Z)-C24 with para-nitro group exhibited the most consistently potent activities against three neoplastic cells, with IC₅₀ ranging from 3.2 to 7.1 μm. Further researches showed that compounds (E,Z)-C24 could induce cell apoptosis and arrest cells cycle at the G2/M and S phases.

Four ligands were dragged out from their MDM2 protein-binding pocket. The differences in free energies calculated by BD-FDT are in agreement with the experimental data. We further found that different binding mechanisms among different ligands are associated with H-bond with Lys51 and Glu25.

A novel efficient algorithm called max–min ant system was designed for solving an assembly of transmembrane proteins. It show noticeably superior convergence performance compared to simulated annealing Monte Carlo and genetic algorithm. The algorithm gives a promising approach for solving structure with low-resolution data.

The antimalarial activity of 3-methoxy-1,2-dioxetanes was determined, and is at a similar level as artemisinin; also, their reactivity towards iron(II) correlate linearly with their antimalarial activity.

The conjugates of hepatoprotective natural compound silybin (SIL) and two natural polyether ionophores monensin (MON) and salinomycin (SAL) displayed interesting antiproliferative activity in various human cancer cells, including MDR cells at low micromolar concentrations. The anticancer activity is connected with high selectivity indexes (SI) and low toxicity against normal cells.

Three series of 5-arylaminouracil derivatives were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the M. tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4‴-hydroxy-2‴-cyclopenten-1‴-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC₉₀ 5 μg/mL).

A series of UA piperazine derivatives were designed and synthesized to improve the anticancer activity and to explore the structure-activity relationships. The effects of the most potent compound 5b on cell proliferation, apoptosis induction and cell cycle were evaluated. Furthermore, we also analyzed the protein-ligand interaction with 5b by using molecular modelling studies.

A series of dihydropyrazole sulfonamide derivatives containing 2-hydroxyphenyl moiety were designed and synthesized as antitumor agent to target the matrix metalloproteinase-2 (MMP-2). All of the synthesized compounds were examined by bioactivity assays, and structure-activity relationship analysis was also performed to discuss how structural changes could impact the bioactivity.

A comparative analysis of pharmacophore features and quantitative structure–activity relationships for CD38 inhibitors with systemic summarizations and analysis given about the binding characteristics and quantitative structure–activity relationships for known CD38 covalent and non-covalent inhibitors, which will be helpful for further CD38 inhibitors design.

A novel series of acridone-1,2,4-oxadiazole-1,2,3-triazole hybrids were synthesized and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities.

Aggregation properties of naturally occurring peptide hemopressin and its 25 synthetic analogs were analyzed using the principle of dynamic light scattering.

We propose a novel strategy by integrating pharmacophore and membrane MD simulations together to improve homology modeling of GPCRs with ligand selectivity. To validate this integrated strategy, the A_2A adenosine receptor (A_2AAR), whose structures in both active and inactive state have been established, has been chosen as an example. This integrated strategy can be further investigated in homology modeling and expand its applicability to other GPCR modeling, which should aid in the discovery of more effective and selective GPCR ligands.

Seventeen novel emodin derivatives were synthesized and the cytotoxic activity were evaluated. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. Compound 9a induced a loss of the mitochondrial transmemberane potential, an increase of reactive oxygen species, release of cytochrome c and activation of caspase 3 and 9.

Three-dimensional activity cliffs derived from X-ray structures were systematically searched for recurrent interaction patterns that distinguished between highly and weakly potent compounds. For different drug targets, interaction hot spots were identified on the basis of detected interaction differences.

We concluded that lentivirus-mediated RNA interference can knock down the expression of IL-1β and TNF-α in joint fluid and, in a synergistic effect when two siRNAs are co-transfected, ease cartilage degeneration. This may indicate a new direction for the use of gene silencing in the treatment of post-traumatic arthritis.

Synergy potential of the indole alkaloids, 1, 2, 4, 5, 9 and a semi-synthetic derivative 9F was deduced by inhibiting efflux pumps and down-regulation of the efflux pump genes. The in silico ADME analysis revealed that some of these alkaloids 1 and 9 are safe, nontoxic and possess good intestinal absorption, which makes them suitable leads for further drug development.

GLP-1 (32–36) amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), retained cell viability and decreased cell apoptosis in vitro and improved glucose disposal in streptozotocin-induced diabetic mice.

A series of novel indole-pyrimidine hybrids were synthesized. All newly synthesized compounds were evaluated for their antiproliferative and tubulin polymerization inhibitory activities. The most promising compound 34 showed more potent and broad-spectrum cytotoxic activities with the IC₅₀ values ranged from 5.01 to 14.36 μm against four cancer cell lines and also displayed the most potent anti-tubulin activity (IC₅₀ = 11.2 μm).

We expanded the application of the ligand efficiency SEI to MLR and CoMFA modeling to investigate the relationships between the hydantoin derivatives and AR antagonist activities. The obtained results indicate that the SEI-based models outperform the pIC₅₀-based models with higher stability, robustness, and predictive abilities. We put forward our opinion that SEI can incarnate the relationships between bioactivities and molecular structures better than pIC₅₀, in nature. SEI could be a more rational parameter to be optimized in the drug discovery.

Covalent docking of the inhibitor 3a with the nsP2 enzyme showing the proposed Michael adduct formed between inhibitors 3a and the side chain of catalytic Cysteine1013.

We introduce novel pyrazolo[4,3-d]pyrimidine 2i, which preferentially inhibits CDK2, CDK5 and aurora A. Treatment with 2i causes the downregulation of cyclins A and B and the dephosphorylation of histone H3 at Ser10, induces apoptosis in HCT-116 cancer cells and reduces angiogenesis-like activity in endothelial cells.

1,2-Diaryl pyrroles as combretastatin A-4 analogues were synthesized and evaluated for anti-proliferative activities. Compound 7q exhibited antitubulin activity.

A facile, fast, environmentally friendly strategy was used to fabricate core–shell magnetic mesoporous silica nanoparticles for pH-triggered anticancer drug delivery.