in silico Modeling of Curcumin Based Sulfonamides Inhibitors of the Human trans-Membrane Carbonic Anhydrase Isozyme, hCA IX by CoMSIA

Carbonic anhydrases, hCAs IX and XII are applied as the markers of progression of the disease in many oxygen deficient tumours and their specially manoeuvred inhibition is directly related to containing the growth of both primary tumours and tumour growth of secondary nature. Ligand-based quantitative structure-activity relationship (QSAR) studies were carried out on curcumin related, sulphonamide derivatives as inhibitors of human trans-membrane carbonic anhydrase isozyme, hCA IX by comparative molecular field similarity analysis (CoMSIA) implemented through the SYBYL package. The capacity of the model to predict coveted compound was evaluated using test set of three compounds. The best model created was found to be of choice as it showed a r2 value of 0.811 and a cross validated coefficient q2 value of 0.617 in tripos CoMSIA hydrophobic region. Results of the present study indicated that hydrophobic region factors play an important role in carbonic anhydrase hCA IX inhibition for compounds.

QSAR STUDIES ON HUMAN CARBONIC ANHYDRASE II INHIBITORS

Carbonic anhydrase II is one of the forms of human α carbonic anhydrases which are ubiquitous metalloenzymes that catalyze inter-conversion of carbon dioxide and water to bicarbonate and proton, overexpression of which leads to disorders such as glaucoma. 2D and 3D Quantitative Structure Activity Relationship studies were carried out on previously synthesized series of sulfanilamide derivatives by VLife MDS software using stepwise variable, multi-linear regression and k-nearest neighbor molecular field analysis methods. 2D-QSAR model depicts contribution of halogens (such as chlorine and fluorine), methylene and oxygen atoms to inhibition of human carbonic anhydrases II activity. Using k-nearest neighbor molecular field analysis method two 3D-QSAR models (model A and B) were generated from which model A was found to be the best validated model with q2 (0.9494), pred_r2 (0.7367) and q2 _ se (0.2037). It displayed the fact that the inhibitory action of sulfanilamide derivatives against human carbonic anhydrases II is influenced by hydrophobicity and electro positivity.

QSAR Studies and Structure Property/Activity Relationships Applied in Pyrazine Derivatives as Antiproliferative Agents Against the BGC823

Electronic structures, the effect of the substitution, structure physicochemical property/activity relationships and drug-likeness applied in pyrazine derivatives, have been studied at ab initio (HF, MP2) and B3LYP/DFT (density functional theory) levels. In the paper, the calculated values, i.e., NBO (natural bond orbitals) charges, bond lengths, dipole moments, electron affinities, heats of formation and quantitative structure-activity relationships (QSAR) properties are presented. For the QSAR studies, we used multiple linear regression (MLR) and artificial neural network (ANN) tatistical modeling. The results show a high correlation between experimental and predicted activity values, indicating the validation and the good quality of the derived QSAR models. In addition, statistical analysis reveals that the ANN technique with (9-4-1) architecture is more significant than the MLR model. The virtual screening based on the molecular similarity method and applicability domain of QSAR allowed the discovery of novel anti-proliferative activity candidates with improved activity.

3D-QSAR Studies of 1,2,4-Oxadiazole Derivatives as Sortase A Inhibitors

Sortase A (SrtA) is an enzyme that catalyzes the attachment of proteins to the cell wall of Gram-positive bacterial membrane, preventing the spread of pathogenic bacterial strains. Here, one class of oxadiazole compounds was distinguished as an efficient inhibitor of SrtA via the “S. aureus Sortase A” substrate-based virtual screening. The current study on 3D-QSAR was done by utilizing preparation of the structure in the Schrödinger software suite and an assessment of 120 derivatives with the crystal structure of 1,2,4-oxadiazole which was extracted from the PDB data bank. The docking operation of the best compound in terms of pMIC ( pMIC = 2.77 ) was done to determine the drug likeliness and binding form of 1,2,4-oxadiazole derivatives as antibiotics in the active site. Using the kNN-MFA way, seven models of 3D-QSAR were created and amongst them, and one model was selected as the best. The chosen model based on q 2 (pred_ r 2 ) and R 2 values related to the sixth factor of PLS illustrates better and more acceptable external and internal predictions. Values of crossvalidation (pred_ r 2 ), validation ( q 2 ), and F were observed 0.5479, 0.6319, and 179.0, respectively, for a test group including 24 molecules and the training group including 96 molecules. The external reliability outcomes showed that the acceptable and the selective 3D-QSAR model had a high predictive potential ( R 2 = 0.9235 ) which was confirmed by the Y -randomization test. Besides, the model applicability domain was described successfully to validate the estimation of the model.

Comprehensive Modeling and Molecular Docking of Phosphodiesterase Inhibitors

In the present study, the biological activity of some pharmaceutical molecules was investigated and predicted by using quantitative structure-activity relationship (QSAR) studies and molecular docking. The aim of this study is to apply QSAR and molecular docking methods to predict and calculate the half maximal inhibitory concentration (IC50) of phosphodiesterase (PDE) 10A. To apply QSAR method at first multiple linear regression (MLR), genetic algorithm (GA), and successive projection algorithm (SPA) were used to select the best descriptors related to PDE 10A inhibitory activity. The selected descriptors were then applied as inputs to construct MLR and a non-linear support vector machine (SVM). Also we used molecular docking method to extract the descriptors and then by using MLR and SVM methods a linear and non-linear models developed respectively. Consequently, a comparison of the results of QSAR and docking study indicated that the non-linear SVM-SPA2 in QSAR study and SVM-MLR in molecular docking study had a much better prediction power than the other models. Finally, the Y-scrambling and cross-validation tests were used to evaluate the validity of the obtained model and the results of these tests indicates that the model is appropriate for using in prediction.

QSAR STUDIES OF SOME SUBSTITUTED IMIDAZOLE DERIVATIVES AS POTENT ANTIFUNGAL AGENTS

Fracture of distal radius is the commonest fracture present in the upper limb. In fact, it is most commonly treated by the doctor. An outstretched hand is the most common cause of distal radius or wrist fractures. The fracture of distal radius can also lead to nerve injury mostly median nerve. Physical Therapy plays important role which provides positive effect in treating post fracture cases. A case of 45 years female is presented in this report who had a fall over right wrist joint and diagnosed with distal radius fracture and operated conservatively results into pain over wrist joint, decrease in physical activities. Rehabilitation protocol is explained below in the report. We report that there were improvement in patient outcomes level increases in muscles strength, provide pain relief and improvement in patient functional Independence.