Docking and QSAR Studies of Camptothecin Derivatives as Inhibitor of DNA Topoisomerase-I

Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme Topoisomerase-I (Topo-I) and has shown remarkable anticancer activity in preliminary clinical trials. The major limitation is its low solubility and high adverse reaction. In the studied work, we performed molecular docking of CPT derivatives against Topo-I and developed the quantitative structure activity relationship (QSAR) model for anticancer activity screening. For QSAR, we used CPT and other anticancer drugs with its IC50 values. We used a total of forty seven anticancer drugs as training set and eight compounds as test set and thirty derivatives of CPT as query set. Total of fifty two chemical descriptors were used for the quantitative data calculation. Only four showed good correlation with the experimental activity. Forward feed regression method was used for development of multiple linear regression (MLR) QSAR model. Model showed acceptable regression coefficient (r2) 0.89 (i.e., 89% of correlation) and cross validation coefficient (rCV2) 0.86 (i.e., 86 % of prediction accuracy). After drug likeness test, ten compounds namely, MSB3a, MSB3b, MSB19, MSB22L, MSB22M, MSB22O, MSB22R, MSB25D, MSB37G and MSB39D, showed promising predicted anticancer activity and drug likeness properties. Out of ten, only six compounds namely, MSB19, MSB22L, MSBM, MSB22O, MSB22R and MSB37D indicate two times more activity than the parent CPT compound. In molecular docking studies, all the identified active CPT derivatives showed high binding affinity with Topo-I. QSAR study indicates that connectivity index, electron affinity, mol.wt. & ether group count highly contribute to inhibitory activity of CPT derivatives. These results can offer useful references for directing the molecular design of Topo-I inhibitor with improved anticancer activity.
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Parametrization of electron impact ionization cross sections for CO, CO2, NH3 and SO2

The electron impact ionization and dissociative ionization cross section data of CO, CO2, CH4, NH3, and SO2, measured in the laboratory, were parameterized utilizing an empirical formula based on the Born approximation. For this purpose an chi squared minimization technique was employed which provided an excellent fit to the experimental data

Generalized Second-Order Duality for a Continuous Programming Problem with Support Functions

A generalized second-order dual is formulated for a continuous programming problem in which support functions appear in both objective and constraint functions, hence it is nondifferentiable. Under second-order pseudoinvexity and second-order quasi-invexity, various duality theorems are proved for this pair of dual continuous programming problems. Special cases are deduced and a pair of dual continuous programming problems with natural boundary values is constructed and it is pointed out that the duality results for the pair can be validated analogously to those of the dual models with fixed end points. Finally, a close relationship between duality results of our problems and those of the corresponding (static) nonlinear programming problem with support functions is briefly mentioned

Synthesis of 2-oxo-azetidine derivatives of 2-amino thiazole and their biological activity

A new series of N-[2-(2-aminothiazolyl)ethyl]-4-(substitutedphenyl)- 3-chloro-2-oxo-1-iminoazetidine, compounds 4(a-m) have been synthesized from 2-aminothiazole as a starting material. The structure of all the synthesized compounds were confirmed by chemical and spectral analyses such as IR, 1H NMR, 13C NMR and FAB-Mass. All the final synthesized compounds 4(a-m) were screened for their antibacterial and antifungal activities against some selected bacteria and fungi and antitubercular activity screened against M. tuberculosis with their MIC value. Antiinflammatory activity screened against albino rats (either sex) and gave acceptable results

Performance Evaluation of GaN based Thin Film Transistor using TCAD Simulation

As reported in past decades, gallium nitride as one of the most capable compound semiconductor, GaN-based high-electron mobility transistors are the focus of intense research activities in the area of high power, high-speed, and high-temperature transistors. In this paper we present a design and simulation of the GaN based thin film transistor using sentaurus TCAD for the extracting the electrical performance. The resulting GaN TFTs exhibits good electrical performance in the simulated results, including, a threshold voltage of 12-15 V, an on/off current ratio of 6.5×107 ~8.3×108, and a sub-threshold slope of 0.44V/dec. Sentaurus TCAD simulations is the tool  which offers study of comprehensive behavior of semiconductor structures with ease. The simulation results of the TFT structure based on gallium nitride active channel have great prospective in the next-generation flat-panel display applications

Molten-Salt-Assisted Annealing for Making Colloidal ZnGa2O4:Cr Nanocrystals with High Persistent Luminescence

Persistent luminescent nanocrystals (PLNCs) in the sub-10 nm domain are considered to be the most fascinating inventions in lighting technology owing to their excellent performance in anti-counterfeiting, luminous paints, bioimaging, security applications, etc. Further improvement of persistent luminescence (PersL) intensity and lifetime is needed to achieve the desired success of PLNCs while keeping the uniform sub-10 nm size. In this work, the concept of molten salt confinement to thermally anneal as-synthesized ZnGa2O4:Cr3+ (ZGOC) colloidal NCs (CNCs) in a molten salt medium at 650 °C is introduced. This method led to significantly monodispersed and few agglomerated NCs with a much improved photoluminescence (PL) and PersL intensity without much growth in the size of the pristine CNCs. Other strategies such as i) thermal annealing, ii) overcoating, and iii) the core–shell strategy have also been tried to improve PL and PersL but did not improve them simultaneously. Moreover, directly annealing the CNCs in air without the assistance of molten salt could significantly improve both PL and PersL but led to particle heterogeneity and aggregation, which are highly unsuitable for in vivo imaging. We believe this work provides a novel strategy to design PLNCs with high PL intensity and long PersL duration without losing their nanostructural characteristics, water dispersibility and biocompatibility

Rare earth free bright and persistent white light emitting zinc gallo-germanate nanosheets: technological advancement to fibers with enhanced quantum efficiency

Recent materials science and engineering research focused on defects, dopants, hosts, and morphological structures has resulted in novel cost efficient and sustainable phases with extraordinary properties and performance. Contributing in this direction we have designed dopant and rare earth free white lightemitting zincgallogermanate (ZGG) phosphors in nanosheet (NS) morphology. These ZGG NSs with interlayer and interfacial defects display bright white photoluminescence (PL) with significant quantum yield (QY). Thermal treatment of the as-synthesized ZGG NSs at 750 1C does not degrade their sheet-like morphology while resulting in long persistent luminescence (PerL) with a duration of approximately one hour. Furthermore, to improve the commercial viability of the as-synthesized ZGG NSs, we have assembled them as fine fibers of polyvinyl alcohol (PVA) using Forcespinnings technology. The ZGG–PVA fibers displayed efficient white PL with increased quantum yield compared to the as-synthesized ZGG NSs. We believe this technological evolution, transitioning from bulk ZGG to ZGG nanosheets, will lead to dopant-free/rare-earth-free persistent white light emission and an enhancement in QY. This technology will be a boon to the optoelectronic and lighting industries, and will benefit commercial applications in smart textiles, energy efficient lighting, night vision, anti-counterfeiting, traffic signals, and security, among other potential uses

Tunable CsPb(Br/Cl)3 perovskite nanocrystals and further advancement in designing light emitting fiber membranes

Cesium lead halide perovskite nanocrystals (NCs) have drawn a great deal of interest in optoelectronic and photonic applications due to their intrinsic and attractive photoluminescence properties. Though, their commercially viability is of concern due to their intrinsic instability. In this study, blue and green luminous PMMA-CsPbX3(X=Cl/Br) fibers were fabricated via forcespinning technique, where the polymer matrix encapsulated the NCs. Blue CsPbX3 NCs (b- CPX NCs) were synthesized at ambient conditions while blue to green CsPbX3 NCs (g-CPX NCs) fine color tuning was obtained after heat treatment at 150°C.Field emission scanning electron microscopy (FESEM) shows fibers with diameters in the single digit microscale. Efficient encapsulation of NCs in the PMMA fiber was confirmed using FTIR spectroscopy. UV visible spectra of the NCs suggested a quantum confinement effect. Pristine NCs shows bright blue and green emission from b-CPX and g-CPX NCs under UV irradiation (365 nm) which was successfully reproduced even upon encapsulation in the PMMA matrix. In both cases, the PMMA besides promoting QD encapsulation also enhanced the photoluminescent quantum yield (PLQY) from 25.5% to 31.1% (blue PMMA fibers) and 42.6% to 51.4% (green PMMA fibers) compare to bare NCs PLQY. The PMMA-CsPbX3(X=Cl/Br) also possessed narrow half-peak width compared to pristine NCs suggesting high color purity. This work provides a novel polymer fiber-based encapsulation approach to solve the intrinsic instability issues of CsPbX3 NCs, therefore prompting promising practical applications

Disorder driven asymmetry and singular red emission in doped Lu2Hf2O7 nanocrystals with no charge compensating defects

High performance luminescent materials possess low symmetry, high color purity, no charge compensating defects, and high quantum yield. In this work, we have synthesized Lu2Hf2O7 (LuHO) and Lu2Hf2O7:Eu3+ (LuHOE) nanocrystals (NCs) using a molten salt synthesis and confirmed that both are stabilized in defect fluorite structure with a high degree of structural disordering. The LuHO NCs depicted green emission under ultraviolet irradiation, which decreases and increases after being treated in oxidizing and reducing environments, respectively, confirming the role of oxygen vacancies in the emission process. The LuHOE NCs (i) show excitation wavelength-dependent host to dopant energy transfer efficiency, (ii) give a singular red emission with high color purity of ~95%, (iii) have a dominant occupation of the Lu3+ sites by Eu3+ ions without the formation of charge compensating defects (CCDs), and (iv) possess low non-radiative channels with a quantum yield of ~88%. We believe these LuHOE NCs with singular red emission, high quantum yield, and color purity acquired through structural disordering and the absence of CCDs warrant further investigation as efficient phosphors

Specialized Metabolites from Ribosome Engineered Strains of Streptomyces clavuligerus

Bacterial specialized metabolites are of immense importance because of their medicinal, industrial, and agricultural applications. Streptomyces clavuligerus is a known producer of such compounds; however, much of its metabolic potential remains unknown, as many associated biosynthetic gene clusters are silent or expressed at low levels. The overexpression of ribosome recycling factor (frr) and ribosome engineering (induced rpsL mutations) in other Streptomyces spp. has been reported to increase the production of known specialized metabolites. Therefore, we used an overexpression strategy in combination with untargeted metabolomics, molecular networking, and in silico analysis to annotate 28 metabolites in the current study, which have not been reported previously in S. clavuligerus. Many of the newly described metabolites are commonly found in plants, further alluding to the ability of S. clavuligerus to produce such compounds under specific conditions. In addition, the manipulation of frr and rpsL led to different metabolite production profiles in most cases. Known and putative gene clusters associated with the production of the observed compounds are also discussed. This work suggests that the combination of traditional strain engineering and recently developed metabolomics technologies together can provide rapid and cost-effective strategies to further speed up the discovery of novel natural products