Synthesis,characterization, biological evaluation and molecular docking studies of 2-(1H-benzo[d]imidazol-2-ylthio)-<Emphasis Type="Italic">N</Emphasis>-(substituted 4-oxothiazolidin-3-yl) acetamides

Background

A series of 2-(1H-benzo[d]imidazol-2-ylthio)-N-(substituted 4-oxothiazolidin-3-yl) acetamides was synthesized and characterized by physicochemical and spectral means. The synthesized compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans and Aspergillus niger by tube dilution method. The in vitro cytotoxicity study of the compounds was carried out against human colorectal (HCT116) cell line. The most promising anticancer derivatives (5l, 5k, 5i and 5p) were further docked to study their binding efficacy to the active site of the cyclin-dependent kinase-8.

Results

All the compounds possessed significant antimicrobial activity with MIC in the range of 0.007 and 0.061 µM/ml. The cytotoxicity study revealed that almost all the derivatives were potent in inhibiting the growth of HCT116 cell line in comparison to the standard drug 5-fluorouracil. Compounds 5l and 5k (IC₅₀ = 0.00005 and 0.00012 µM/ml, respectively) were highly cytotoxic towards HCT116 cell line in comparison to 5-fluorouracil (IC₅₀ = 0.00615 µM/ml) taken as standard drug.

Conclusion

The molecular docking studies of potent anticancer compounds 5l, 5k, 5i and 5p showed their putative binding mode and significant interactions with cyclin-dependent kinase-8 as prospective agents for treating colon cancer.

     

Dynamics of a stochastically driven Brownian particle in one dimension

We present a study on the dynamics of a system consisting of a pair of hardcore particles diffusing with different rates. We solved the drift-diffusion equation for this model in the case when one particle, labeled F, drifts and diffuses slowly toward the second particle, labeled M. The displacements of particle M exhibits a crossover from diffusion to drift at a characteristic time which depends on the rate constants. We show that the positional fluctuation of M exhibits an intermediate crossover regime of subdiffusion separating initial and asymptotic diffusive behavior; this is in agreement with the complete set of Master Equations that describe the stochastic evolution of the model. The intermediate crossover regime can be considerably large depending on the hopping probabilities of the two particles. This is in contrast to the known crossover from diffusive to subdiffusive behavior of a tagged particle that is in the interior of a large single-file system on an unbound real line. We discuss our model with respect to the biological phenomena of membrane protrusions, where polymerizing actin filaments (F) push the cell membrane (M).     

A Novel High Throughput Method to Investigate Polymer Dissolution

The dissolution behavior of polystyrene (PS) in biodiesel was studied by developing a novel high throughput approach based on Fourier‐transform infrared (FTIR) microscopy. A multiwell device for high throughput dissolution testing was fabricated using a photolithographic rapid prototyping method. The dissolution of PS films in each well was tracked by following the characteristic IR band of PS and the effect of PS molecular weight and temperature on the dissolution rate was simultaneously investigated. The results were validated with conventional gravimetric methods. The high throughput method can be extended to evaluate the dissolution profiles of a large number of samples, or to simultaneously investigate the effect of variables such as polydispersity, crystallinity, and mixed solvents.

     

Extended Kalman filter for modal identification of structures equipped with a pendulum tuned mass damper

Pendulum tuned mass dampers (PTMDs) have been employed in several full-scale applications to attenuate excessive structural motions, which are mostly due to wind. Conducting periodic condition assessments of the devices to ascertain their health is necessary to ensure their continued optimal performance, which involves identifying the modal parameters of the underlying (bare) structure to which they are tuned to. Such an identification is also necessary for the design of control systems such as adaptive tuned mass dampers. Existing methods of arresting the motion of the damper to estimate the modal properties are expensive, time-consuming, and not suitable for online tuning. Instead, in this paper, parameter estimation using the Extended Kalman Filter (EKF) is proposed to undertake this task. The central task accomplished here is to estimate the dynamic characteristics of the bare structure (structure without the PTMD) from response measurements of the coupled main structure and PTMD system. The proposed methodology relies on ambient acceleration measurements of TMD-attenuated responses to estimate the bare structural modal frequencies, damping, and mode shapes, which can then be used either for condition assessment or for control. The application of EKF to modal parameter estimation is not new. However, a methodology to address the problem in wind engineering arising from stochastic disturbances present in both the measurement and state equations, and unknown process and noise covariances arising due to ambient excitations, is presented for the first time. Extensively studied for synthetic data, these two challenges have limited thus far the application of Kalman filtering to practical wind engineering parameter estimation problems using experimentally obtained measurements. In this paper, a detailed methodology is presented to address these challenges by using a modified form of the standard EKF equations, together with an algorithm to estimate the unknown disturbance and measurement noise covariances. Numerical simulations and an experimental study are both presented. Results demonstrate that the method proposed provides reliable estimates for the modal parameters required to perform condition assessment and control tasks for pendulum tuned mass dampers.     

Studies on the Preparation of 113Sn-113mIn Generators

Presently available ^113mSn.^113mIn generators use high specific activity ¹¹³Sn which cannot be produced in low and medium flux research reactors even with enriched ¹¹²Sn. This paper describes a method of preparing ¹¹²Sn.^113mIn generators using ^ll3Sn of relatively low specific activity (2—3 Ci/g) obtained by irradiation of enriched ¹¹²Sn in CIRUS. In this modified procedure, ¹¹³SnCl₄ is firmly adsorbed on hydrous zirconia from 3—4 M NaCl solutions of pH 1.3 to 1.5 and the elution of ^113mIn is effected by dilute HCl. The generator yields 70% of the theoretically available ^ll3mIn activity. ¹¹³Sn breakthrough has been consistantly less than 0.01% of the ^113mIn activity. Stable zirconium contamination in the eluate has been estimated to be less than 1 ppm. The performance characteristics of different varieties of hydrous zirconia have been studied to evaluate the optimum tin loading, indium elution and soluble zirconium contamination. Generators containing upto 700 mCi of tin-113 have been prepared yielding pure indium-113m suitable for medical use.     

Electron momentum distributions and compton profiles of some molecules with FSGO model

The electron momentum distributions and the Compton profiles (within the impulse approximation) of H₂, LiH, methane, water, acetylene, ethylene, ethane cyclopropane and cyclobutane have been calculated using the floating spherical Gaussian orbital (FSGO) wavefunctions. The agreement of the single-FSGO Compton profiles with the corresponding experimental or the Hartree-Fock (HF-SCF) theoretical ones is fairly good in most of the cases examined. The advantages and drawbacks of using the FSGO model for the calculation of Compton profiles are discussed.     

Polarographic speciation of copper(II) in the presence of 1-dimethylaminopropan-2-ol

Volatile amines are used in boiler-water treatment and their performance is judged not only from two main factors, viz., basicity and volatility, but also from their thermodynamic stability, metal complexation capacity and interaction with ion-exchange systems. The complexation of copper by 1-dimethylaminopropan-2-ol was studied. Its pK_b value was found to be 4.5 at 25°C. It formed a coloured complex in the pH range 8.5–10.5 and its log K value was found to be 18.2.