Docking

New Chemical Entities (NCEs) were designed using information from pharmacophore profile of known anticonvulsants. Binding affinities of designed NCEs were studied on gamma-aminobutyric acid (GABA-alpha) using docking studies. Two Dimensional (2D) Quantitative Structure–Activity Relationship (QSAR) studies were performed for correlating the chemical composition of triazolethione analogs and estimation of their anticonvulsant activity using Multiple Linear Regression (MLR) Analysis.  ADMET properties were also predicted. These four basic strategies (pharmacophore mapping, QSAR, docking & ADMET screening) were implemented to evaluate the performance of derivatives. Although predicted Ki through QSAR model showed significant mild activity for GABA. Conclusively compounds, 2, 6, 7, 8, 9, 10, 11, and 20 were observed to be most feasible to activate GABA for anticonvulsant activity.

The present study deals with docking of Hematoporphrin with various anticancer drugs targeting enzymes. The targets used were PDB-ID 2Y3I, PDB-ID 3OZZ, PDB-ID 3UEN and PDB-ID 4O33. Hematoporphyrin docked with these enzymes and interactions between the enzyme and compound were measured and compared with standard Paclitaxel. The study concluded that, the compound (Hematoporphyrin) isolated from plant were high interactions with PDB-ID 4O33 when compared to standard.

A series of pyridinamide-containing naproxen derivatives were synthesized through different routes starting with naproxenoyl chloride (2) which, upon reaction with 2-or 3-aminopyridine, gave the corresponding naproxenamide derivatives 3a,b. Also, urea derivatives 5a,b were obtained through the reaction of compound 2 with sodium azide followed by reaction with 2-or 3-aminopyridene via Curtius rearrangement. In addition, naproxenoyl isothiocyanate was synthesized and reacted with 2- or 3-aminopyridine, where the thiourea derivatives 7a,b were obtained. Furthermore, cyanoacetanilide 9 was synthesized and reacted with acetylacetone, arylidenemalononitriles or arylidenecyanoacetate to furnish the corresponding pyridine amide derivatives 10-13. All compounds were screened for anti-inflammatory activity using an in vivo rat paw edema model, from which six of them exhibited higher potency than naproxen. The ulcerogenic effect of most of the active compounds was also screened. In ulcerogenicity screening, the potent anti-inflammatory compounds 3b, 5a and 5b were devoid of any ulcerative effect. This is contrary to naproxen which caused 100% ulcerative effect on all tested animals. Structure-based molecular modeling described that the virtual screening agrees with the SAR of in vivo anti-inflammatory and ulcerogenic activities. Furthermore, all the synthesized compounds were screened for their anti-microbial activity.

A Molecular docking study on novel Acetamide derivatives as specific Mono amino oxidase (MAO) A inhibitory agents was performed with a set of 40 compounds to analyze their inhibitory action.  For this, compounds were designed on the basis of available literature and used as Ligands for molecular interaction. The structure of molecular target Mono Amino Oxidase A (MAO A) was retrieved from the PDB database (PDB ID 2Z5X). For comparative analysis Clorgyline, a well-known specific MAO A inhibitor was taken as the standard. Computational docking analysis was performed using PyRx, AutoDock Vina option based on scoring functions. Among 40 compounds the top 11 hits were recognized as promising MAO A inhibitors, according to their docking scores and selected for further study of interaction and visualization. Phenyl sulphanyl derivative with chlorobenzyl amino moiety (Code AD31) showed an optimum binding affinity and stable complex with a molecular target MAO A  with the binding energy of -8.3  kcal/mol as compared to the standard (-7.6 kcal/mol). These results indicated that proposed modification in Acetamide derivatives may produce potent and specific MAO A inhibitors to treat depression with lesser side effects.

Tuberculosis is a serious threat to public health throughout the world. Schiff bases are compounds carrying the imine or azomethine (–C=N–) functional group. Recent studies report that benzimidazole based Schiff bases possess antibacterial, antimicrobial, anti-tubercular, and anti-inflammatory activities. 1,2 Further it has been known that fluoroaniline moiety can have profound and unexpected results in biological activity 19. A series of benzimidazole and fluroaniline based Schiff bases were designed and docked against crucial mtb enzyme target Glutamine synthetase1. The molecules with good docking-score and multiple interactions were chosen for synthesis. Compounds (BE1, BE2, FA-1, FA-2, and FA-3) were synthesized by reflux condensation reaction with good yield. The newly synthesized compounds were characterized by spectral methods and evaluated for anti- mycobacterial activity against tuberculosis H37RV strain. Anti-tubercular activity was carried out by using Microplate Alamar Blue Assay (MABA) method. The experimental results revealed that Compounds (BE1& BE2) showed promising anti-tubercular activity with an MIC below 0.8 mcg/mL while (FA-1, FA-2, and FA-3) showed moderate anti tubercular activity with an MIC below 6.25 and 12.5 mcg/mL. Key words: Benzimidazole, Schiff base, Fluoroaniline, Docking, Anti-tubercular.

In the present study structure based virtual screening of compound data base, prediction of activity of high extra precision glide docking scored (XPGS) molecules by atom based 3D QSAR model, XP glide docking analysis of known inhibitors to know the key residue interactions and ADME study of identified Histone Deacetylase 2 (HDAC2) inhibitors were performed. A 3D QSAR model was build for both training set (R2 = 0.9867, SD= 0.104, F= 322.1 and N= 17) and test set (Q2 = 0.9137, Pearson r= 0.9671, RMSE = 0.160, N = 7) molecules and showed a statistically significant and good predictive model. The visualization of 3D QSAR model suggested that introduction of hydrogen bond donor group in 5-position of pyridine ring, 6-position of 1,2-diaminobenzene ring; hydrophobic groups in the 2,4-position of pyridine ring, 5,6 -position of 1,2-diamino benzene ring, 2,3,5,6-position of amonomethylbenzamide ring of highest active compound 1 were suitable to increase the HDAC2 inhibitory activity. The XP glide docking analysis of the known inhibitors showed that residues PHE-155, Gly-154, His-145, His-146, Asp-104 and Zn-ligand interaction in the active site region play a crucial role for inhibitory activity. The activity of high glide scored molecules resulted from virtual screening were predicted by atom based 3D QSAR model. After prediction of activity the molecules were subjected to ADME study to know the drug likeness properties and reported 10 molecules having XPGS > 12.0 and predicted activity > 6.7 as potent HDAC2 inhibitors. The docking interaction of known inhibitors was also similar to the docking interaction of identified ten potent inhibitors.