Enantioselective aldol reactions with fluoroacetate would enable access to numerous fluorinated analogues of therapeutically important compounds but have been a long-standing unsolved challenge. Now, bioinspired fluoromalonic acid half thioesters (F-MAHTs) have been devised and allow for highly stereoselective reactions with aldehydes under mild organocatalytic conditions.

Enantioselective aldol reactions with masked fluoroacetates

Synthesis, antiviral activity, 3D-QSAR, and interaction mechanisms study of novel malonate derivatives containing quinazolin-4(3H)-one moiety

Alzheimer's disease is characterized using amyloid-beta (Aβ) aggregation. The present work was carried out to extend and design a novel quantitative structure-activity relationship (QSAR) model on inhibition efficiency of some of new 2-arylethenylquinoline derivatives against the Aβ1-42 peptide aggregation. The QSAR study, molecular docking and molecular dynamics (MD) simulations were performed to explore the influence of the structural features and investigate the molecular mechanism of ligands interactions with the Aβ1-42 peptide. Using molecular docking was understood that electron donating groups with small size help to create interactions between the ligands and peptide residues to stabilize the conformation of ligands at the binding pocket. QSAR model was developed using the most stable conformations and parameters that obtained from the molecular docking. It is shown that, a combination of docking parameters and structural descriptors of inhibitor compounds can describe the inhibition efficiency on Aβ1-42 peptide. The model exhibited statistically significant results so that the coefficient of determination R2train, Q2LOO, R2ext and GH (goodness of hit) are 0.912, 0.915, 0.836 and 0.804, respectively. The stability and binding modes of the compounds 1 and 13 with the most inhibition efficiency and compounds 12 and 36 with the lowest inhibition efficiency were determined by molecular dynamics simulations in GROMACS package. It is showed that interactions of compounds 1 and 13 are stable after 25ns of trajectories. Based on obtained results, 10 new drug compounds have been designed that provide better inhibition efficiency with the Aβ1-42 peptide than the reference compounds.

Molecular docking, molecular dynamics simulations and QSAR studies on some of 2-arylethenylquinoline derivatives for inhibition of Alzheimer's amyloid-beta aggregation: Insight into mechanism of interactions and parameters for design of new inhibitors.

3D-QSAR, molecular dynamics simulations and molecular docking studies of benzoxazepine moiety as mTOR inhibitor for the treatment of lung cancer.

A bicatalyzed three-component cascade between simple aliphatic enolizable aldehydes, a fluorine source, and keto acids has allowed the diastereoselective and enantioselective direct synthesis of carbonyl-elongated vicinal fluorohydrins. The obtained complex acyclic functionalized molecules, possessing up to four stereogenic centers controlled in usually >95% ee, hold great promise for further synthetic developments and rapid incorporation in bioactive elaborated structures.

https://hal.archives-ouvertes.fr/hal-01687102/document

Bicatalyzed Three-Component Stereoselective Decarboxylative Fluoro-Aldolization for the Construction of Elongated Fluorohydrins

Molecular modeling studies of atorvastatin analogues as HMGR inhibitors using 3D-QSAR, molecular docking and molecular dynamics simulations

The activities of a cyclohexene series of influenza neuraminidase inhibitors were studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics methods. The 3D-QSAR models were established by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods. The optimum CoMFA and CoMSIA models yielded satisfactory statistical results: the leave-one-out cross-validation correlation coefficients (q
 2) were 0.722 and 0.779, respectively. The corresponding non-cross-validated r
 2 were both 0.996. Based on the built 3D-QSAR models, several new neuraminidase inhibitor analogs were designed. Molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket of neuraminidase protein. Molecular dynamics simulation further determined the binding process and validated the rationality of docking results. .

/pdf/combined-3d-qsar-molecular-docking-and-molecular-dynamics-3znfvpp9h5.pdf

Zhi Wang

Papers

Molecular modeling studies of atorvastatin analogues as HMGR inhibitors using 3D-QSAR, molecular docking and molecular dynamics simulations

Combined 3D-QSAR, molecular docking, and molecular dynamics study on potent cyclohexene-based influenza neuraminidase inhibitors

3D-QSAR and Docking Studies on 2-acyliminobenzimidazoles Derivatives as Potent ALK Inhibitors