Multi-targeted molecular docking,drug-likeness and ADMET studies of derivatives of few quinoline- and acridine-based FDA-approved drugs for anti-breast cancer activity

Structural Chemistry - Quinoline- and acridine-based drugs are widely used as anti-breast cancer agents. These drugs act through various mechanisms of action; for example, neratinib acts on...     

Aqueous microwave-assisted DMAP catalyzed synthesis of β-phosphonomalonates and 2-amino-4H-chromen-4-ylphosphonates via a domino Knoevenagel-phospha-Michael reaction

An aqueous microwave (mw)-assisted DMAP catalyzed one-pot highly efficient route to synthesize β-phosphonomalonates and 2-amino-4H-chromen-4-yl phosphonates has been demonstrated via the domino Knoevenagel-phospha-Michael reaction of aryl aldehyde/salicylaldehyde, malononitrile/ethyl cyanoacetate and alkyl phosphite ester. Optimization of reaction conditions were performed by using conventional and microwave synthetic approaches. This conversion proceeded smoothly to deliver the desired product in good to excellent yields (75–95%) in a short reaction time (10–12 min). The present methodology is very simple, environmentally benign, high yielding and has very well demonstrated the synergistic effect of water and microwaves.     

Similarity of L-fuzzy Relations Based on L-topologies Induced by L-fuzzy Rough Approximation Operators

This paper proposes similarity of L-fuzzy relations based on L-topologies induced by L-fuzzy rough approximation operators. First, the notion L-fuzzy rough set is generalized and the relationship between generalized L-fuzzy rough sets and L-topologies on an arbitrary universe is investigated. It shows that Alexandrov L-topologies can be induced by L-fuzzy relations without any preconditions. Second, the concept of similarity of L-fuzzy relations is introduced and variations of an L-fuzzy relation are investigated. Third, algebraic structures on similarity of L-fuzzy relations are obtained. Finally, we prove that the subset of the transitive L-fuzzy relations similar to a fixed L-fuzzy relation is a complete distributive lattice.     

Fluidization characteristics of sawdust in a cold flow fluidized bed

India has abundance of biomass such as rice husk, bagasse, wheat straw, sawdust etc. which is used as a main or auxiliary fuel in the fluidized bed combustor, gasifier and pyrolizer. Design of such fluidized bed equipments require the knowledge of minimum fluidization velocity (U_mf), complete fluidization velocity (U_cf) and transport disengagement height (TDH). The present work reports the fluidization characteristic, U_mf, U_cf and TDH of the individual size groups of sawdust and mixture thereof. The results indicate that the U_mf and U_cf have a tendency to increase with increase in particle diameter, however the TDH shows the reverse trend. The sawdust particle size of 925 and 1200 ​μm showed significant difference between their U_mf and U_cf, an essential parameter for controlled fluidization. Based on the experimental work new correlations for the prediction of U_mf, U_cf and TDH for sawdust sample are proposed. The proposed correlations of U_mf, U_cf and TDH are in good agreement with experimental values and the deviations found within the range of nearly ±10% for all the samples.     

Molecular structural investigations of quinoxaline derivatives through 3D-QSAR,molecular docking,ADME prediction and pharmacophore modeling studies for the search of novel antimalarial agent

In the present article, a dataset of 63 quinoxaline derivatives were taken for antimalarial activity and pharmacophore were developed. Atom based method was used to develop a three dimensional quantitative structure activity relationship (3D-QSAR) model. On comparison of all statistical parameters, model AHRRR23 was found to be the most effective and predictive QSAR model as it satisfied all statistical parameters of a good model. The model AHRRR23 showed an adequate R² value for the training set 0.9446, good predictive power with Q² of 0.6409, good F- value, low SD 0.1218 value and outstanding Pearson-R values and low RMSE 0.2779 values of the model. The docking studies also gives very good results with good RMSD values. 3D QSAR, docking and ADME studies exhibits that the developed model could be employed as a potential lead for further study as antimalarial drug.     

Pressure induced phase transitions in Ga1 − x In x P

We have theoretically investigated the effect of pressure on the structural stability of GaP?:?InP mixed system. The three-body-potential (TBP) model has been used. The TBP model consists of long-range as well as short-range interactions; the long-range part includes the modified Coulomb force as well as a three-body term; the short-range part in TBP defines the van der Waals and overlap repulsive interactions. We observe a pressure-induced structural phase transformation from ZnS (B3) to NaCl (B1) type phase in Ga _1?x In _x P. Our calculated transition pressures for the initial GaP and final InP compound semiconductors are in good agreement with other reported data.     

Thermoluminescence characteristics of inorganically and organically capped ZnS:Cu nanophosphors

ZnS:Cu nanophosphors were prepared by wet chemical methods and characterized by X-ray diffraction (XRD). The typical morphologies of the nanophosphors were investigated by scanning electron microscopy (SEM). The thermoluminescence (TL) properties of inorganically and organically passivated ZnS:Cu nanophosphors were investigated after γ-irradiation using a ⁶⁰Co source at room temperature. The TL glow curve of capped ZnS:Cu showed variation in TL peak and intensity as the capping agent was changed. Amongst the synthesized samples the TL glow curve of SiO₂ capped ZnS:Cu showed the highest TL intensity. It has been found that TL response of SiO₂ capped ZnS:Cu is linear in the range 10-550 Gy. A discussion of the obtained results is also presented.     

ZnO nanoparticles: a green efficient catalyst for the room temperature synthesis of biologically active 2-aryl-1,3-benzothiazole and 1,3-benzoxazole derivatives

A facile synthetic protocol for the synthesis of 2-aryl-1,3-benzothiazoles and 1,3-benzoxazoles has been demonstrated using ZnO nanoparticles as a mild and efficient heterogeneous catalyst. The reactions using ZnO nanoparticles were very fast (<8 min) and provided excellent yields (>90%) of the products. The catalyst was recycled and reused up to eight times without significant loss of catalytic activity. The potential application of 2-(4-hydroxyphenyl)-1,3-benzothiazole as new acid–base indicator has also been demonstrated in this Letter.     

Design and pharmacophoric identification of flavonoid scaffold-based aromatase inhibitors

Aromatase is a crucial enzyme for the catalysis of aromatization reaction at the last and rate-limiting step involved in the conversion of androgenic substrates to an estrogenic substrate. A hormone-dependent breast cancer in postmenopausal woman can be cured by inhibition of estrogen biosynthesis by the help of aromatase inhibitors (AIs). The mode of interactions of flavonones with the active site of aromatase has been studied in search of potent and selective AIs as a substitute of the natural steroidal ligand. Structure-based computational approach namely, molecular docking simulations were performed to investigate the structural features of the docked complex of aromatase and flavonoid ligands. A nonsteroidal flavonoid pharmacophore showing electrostatic and steric features for selective binding within the main pocket of the catalytic active site of aromatase has been identified as an outcome of the study. The binding affinity of quercetin and isoflavone were predicted within aromatase. Isoflavone was used as a negative control to compare its binding affinities with the selected dataset. The predicted binding affinity of negative control isoflavone was in accordance with its in vitro AI efficacy. Isoflavone showed poor binding affinity and ranked last in terms of MolDock score (−86.309 kcal/molÅ) compared to dataset molecules. The generated pharmacophoric information will be helpful for the synthetic chemist to design and synthesize selective AIs with comparable binding affinity to the natural steroidal ligand.     

Theoretical and experimental vibration analysis of an oblique space frame

This paper has the general objectives of relating analytical and experimental techniques for analysis of indeterminate spatial frames under dynamic loading. The model used has been made as general as possible to explore validity for nonstereotyped configurations. A highly redundant oblique four-bar space frame was selected having a lowest natural frequency of 42.1 cps. Recent success of the finite-element-matrix method and progress in the field of nonlinear optimization provides a rational basis for the synthesis of space frames; however, the validity of the discretization, both for strength-stiffness analysis and dynamic analysis, has not been explored for this type of configuration. The flexibility influence coefficients, the natural frequencies and the steady-state vibration amplitudes were experimentally determined and compared with theoretical values. Influence coefficients had an “error” of between four and 10 percent; the six lowest natural frequencies were in agreement within 15 percent when rotary inertia was considered. Steady-state amplitudes were in good agreement at frequencies not too close to resonance.