-Tosyl Hydrazone Benzopyran, a New Ligand of PPARα Obtained from Mapping the Conformational Space of Its Active Site.

We report here a new ligand for the peroxisome-proliferator-activated receptor type α (PPARα), an N-tosyl hydrazone benzopyran that was designed throughout the mapping of the polar zone of the binding site of PPARα; such a compound displays a strong activity on this receptor that is comparable to that of the reference compound WY-14643. For the design of the -tosyl hydrazone benzopyran, we have carried out an exhaustive conformational study of WY-14643 and a previously reported hydrazine benzopyran derivative using conformational potential energy surfaces (PES). This study allowed us to map in a systematic way the entire binding site of the PPARα.

Antinociceptive effect of cyclic and linear diterpenoids as new atypical agonists of κ-opioid receptors obtained from four species of the Baccharis genus, and vehiculated in nanometric niosomes.

New natural analgesic compounds that act in KORs are important alternatives for potential therapeutical use in medicine. In this work, we report and compare here the antinociceptive activity displayed by cyclic and linear diterpenes, obtained from the genus Baccharis. The antinociceptive activities determined were relatively strong, in comparison whit morphine.

Evaluating the conformational space of the active site of D dopamine receptor. Scope and limitations of the standard docking methods.

We report here for the first time the potential energy surfaces (PES) of phenyletilamine (PEA) and meta-tyramine (m-OH-PEA) at the D dopamine receptor (D2DR) binding site. PESs not only allow us to observe all the critical points of the surface (minimums, maximums, and transition states), but also to note the ease or difficulty that each local minima have for their conformational inter-conversions and therefore know the conformational flexibility that these ligands have in their active sites. Taking advantage of possessing this valuable information, we analyze how accurate a standard docking study is in these cases.

Quinazoline-tethered hydrazone: A versatile scaffold toward dual anti-TB and EGFR inhibition activities in NSCLC.

Globally, lung cancer and tuberculosis are considered to be very serious and complex diseases. Evidence suggests that chronic infection with tuberculosis (TB) can often lead to lung tumors; therefore, developing drugs that target both diseases is of great clinical significance. In our study, we designed and synthesized a suite of 14 new quinazolinones (5a-n) and performed biological investigations of these compounds in Mycobacterium tuberculosis (MTB) and cancer cell lines.

Conformational and electronic study of dopamine interacting with the D dopamine receptor.

We report an exhaustive conformational and electronic study on dopamine (DA) interacting with the D dopamine receptor (D DR). For the first time, the complete surface of the conformational potential energy of the complex DA/D DR is reported. Such a surface was obtained through the use of QM/MM calculations.

Antinociceptive effect of neo-clerodane diterpenes obtained from Baccharis flabellata.

We report here for the first time antinociceptive effects of extracts from Baccharis flabellata. Two extracts in this analysis, one obtained in summer and the other during winter time. Our results indicate that both extract show strong antinociceptive effects, being the extracts obtained during the summer significantly more active.

Molecular modeling study of dihydrofolate reductase inhibitors. Molecular dynamics simulations, quantum mechanical calculations, and experimental corroboration.

A molecular modeling study on dihydrofolate reductase (DHFR) inhibitors was carried out. By combining molecular dynamics simulations with semiempirical (PM6), ab initio, and density functional theory (DFT) calculations, a simple and generally applicable procedure to evaluate the binding energies of DHFR inhibitors interacting with the human enzyme is reported here, providing a clear picture of the binding interactions of these ligands from both structural and energetic viewpoints. A reduced model for the binding pocket was used.

Searching the "biologically relevant"conformation of dopamine: a computational approach.

We report here an exhaustive and complete conformational study on the conformational potential energy hypersurface (PEHS) of dopamine (DA) interacting with the dopamine D2 receptor (D2-DR). A reduced 3D model for the binding pocket of the human D2-DR was constructed on the basis of the theoretical model structure of bacteriorhodopsin. In our reduced model system, only 13 amino acids were included to perform the quantum mechanics calculations.

Ab initio and DFT study of the conformational energy hypersurface of cyclic Gly-Gly-Gly.

The multidimensional conformational potential energy hypersurface (PEHS) of cyclic Gly-Gly-Gly (1,4,7-triazonane-2,5,8-trione) was comprehensively investigated at the Hartree-Fock (RHF/6-31G(d)) level of theory. The equilibrium structures, their relative stability, and the transition state (TS) structures involved in the conformational interconversion pathways were analyzed. aug-cc-pVTZ//B3LYP/6-311++G** single point calculations predict a trans-cis-cis conformation as the energetically preferred form for this compound.