The cover picture shows that a multistep framework is developed with the ultimate goal of identifying novel herbicides. Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is one of the most significant targets for herbicide design. Using the crystal structure of tobacco mitochondrial PPO (mtPPO) as template, inhibitors were docked into the active site. The docking pose of each compound was subsequently used in a receptor-based alignment, leading to the development of a significant CoMFA model with r² value of 0.98 and q² (cross validation r²) value of 0.63. This novel multistep framework gives insight into the structural characteristics for the binding of inhibitors. In addition, the simplicity of the proposed approach may be particularly applicable in virtual screening procedures. More details are discussed in the article by Yang et al. on page 1153–1158.

Some important aspects of molecular similarity are reviewed in this paper, including the implementations of various similarity evaluation methods, summaries and characteristics of a number of molecular databases, different performance evaluation metrics, etc.

This class of compounds are not effective binders of anti-apoptotic Bcl-2 family proteins. Their apoptosis-inducing effects are possibly due to BAX activation rather than Bcl-2 inhibition as suggested by a recent study.

Two isomers of iodiconazole, a novel antifungal agent, were prepared by asymmetric synthesis. Their antifungal activity and binding modes were investigated.

The structure of CCR4 based on bovine rhodopsin was built through homology modeling. And six tri-substituted chiral pyrrolidin-2-one derivatives have been designed and synthesized as CCR4 antagonists. Several of these compounds show high inhibitory effect in cell assays and higher affinity for the N-terminal of CCR4. Among the compounds, 1c exhibited excellent activity.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is one of the most significant action targets for a large and chemically diverse family of inhibitors that may be used as herbicide, bactericide, fungicide, or photosensitizing activator to treat cancer through photodynamic therapy (PDT). Molecular docking and 3D-QSAR CoMFA were combined in a multistep framework with the ultimate goal of identifying important factor contributing to the activity of PPO inhibitors. This novel multistep framework gives insight into the structural characteristics that affect the binding and the inhibitory activity of these analogues on PPO with different kinds of structural framework, and it can be extended to other classes of PPO inhibitors. In addition, the simplicity of the proposed approach may be particularly applicable in virtual screening procedures.

The secretory phospholipase A2 (sPLA2) and sphingomyelin (SMS) are the key enzymes to atherosclerosis. In this paper, we combined the single sPLA2 and SMS inhibitors with a carbon chain to get a series of dual inhibitors. The biological evaluation showed these compounds had the moderate inhibition against both enzymes.

MB-QSAR models were constructed in acetohydroxyacid synthase mutants to predict and elucidate the molecular herbicide resistance against chlorsulfuron.

In the present study, a series of triazole and benzotriazole derivatives as novel p90 ribosomal S6 protein kinase 2 (RSK2) inhibitors were designed and synthesized. The in vitro activities of the 14 compounds against RSK2 were evaluated, among which, compounds 5, 6, 11, 12, 13 and 14 exhibited enzyme IC₅₀ values of 8.91, 2.86, 3.19, 3.05, 4.49 and 2.09 µmol/L respectively. The proposed binding modes were simulated using molecular docking method, and the docking results coupled with the structure-activity relationship (SAR) analysis indicated that all our active compounds bound to the RSK2 ATP binding site at NTKD, and the electron-donating groups on the 4-position of phenyl were the key point for the inhibitory activity.

Quinolinone derivatives were selected via virtual screening, and they were synthesised and tested for SARS CoV 3CL^pro enzymatic inhibition in vitro. Compound 23 showed the most potent inhibitory activity (IC₅₀=36.86 nmol/L). The binding model was also discussed using docking studies.

A series of 6-modified 2′,3′-dideoxyguanosine and 2′,3′-didehydro-2′,3′-dideoxyguanosine analogs were synthesized. Anti-HIV activity was investigated in cell-based assay. ddGTP was synthesized as well as D4TTP by a novel "one-pot" method, and the incorporation efficiencies recognized by DNA polymerase and HIV reverse transcriptase (HIV RT) were evaluated.

A hydroxylation reaction mechanism of the antipsychotic drug in the active site of CYP2D6 was studied by ONIOM methods, which describes the conversion of aripiprazole from an active form to an inactive 4-hydroxylated form.

A series of 3-N-aryloxyethyl substitutional isoconessimine derivatives were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors. All of the synthesized derivatives exhibited potential anti-acetylcholinesterase activities with IC₅₀ values at micromolar to sub-micromolar range. 7b showed the most potent inhibitory activity with an IC₅₀ of 110 nmol/L. The molecular docking results showed that 7b can be well docked into the active site of acetylcholinesterase.