New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents: Key Computational Insights.

An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2-4 h) with an 80-85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC50 values between 7.5 and 11.1 µM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.

Evaluation of Anticancer and Anti-Mitotic Properties of Quinazoline and Quinazolino-Benzothiadiazine Derivatives.

BACKGROUND: Cancer is one of the major health and social-economic problems despite considerable progress in its early diagnosis and treatment. Owing to the emergence and increase of multidrug resistance to various conventional drugs, and the continuing importance of health-care expenditure, many researchers have focused on developing novel and effective anticancer compounds. OBJECTIVE: Chemical repositories provide a good platform to evaluate and exploit known chemical entities for the identification of other biological activities. In the present study, we have selected an in-house library of synthesized compounds based on two different pharmacophoric scaffolds to evaluate their cytotoxic potency on various cancer cell lines and mechanisms of action. METHODS: A series of in-house synthesized quinazoline and quinazolino-benzothiadiazine derivatives were investigated for their anticancer efficacy against a panel of five cancer (DU145, MCF7, HepG2, SKOV3 and MDA-MB-231) and one normal (MRC5) cell lines. Furthermore, the active compound of the study was investigated to elucidate the mechanism of cytotoxicity by performing series of experiments such as cell cycle analysis, inhibition of tubulin polymerization, alteration of mitochondrial membrane potential, determination of endocytic pathway for drug uptake pathway and combination drug treatment. RESULTS: Among all the tested compounds, fifteen of them exhibited promising growth-inhibitory effect (0.15- 5.0µM) and induced cell cycle arrest in the G2/M phase. In addition, the selected compounds inhibited the microtubule assembly; altered mitochondrial membrane potential and enhanced the levels of caspase-9 in MCF-7 cells. Furthermore, the active compound with a combination of drugs showed a synergistic effect at lower concentrations, and the drug uptake was mediated through clathrin-mediated endocytic pathway. CONCLUSION: Our results indicated that quinazoline and quinazolino-benzothiadiazine conjugates could serve as potential leads in the development of new anticancer agents.

Facile synthesis of light harvesting semiconductor bismuth oxychloride nano photo-catalysts for efficient removal of hazardous organic pollutants.

In the present work, bismuth oxychloride nanoparticles-a light harvesting semiconductor photocatalyst-were synthesized by a facile hydrolysis route, with sodium bismuthate and hydroxylammonium chloride as the precursor materials. The as-synthesized semiconductor photocatalysts were characterized using X-ray diffraction analysis, Fourier transform infra-red spectroscopy, Raman spectroscopy, Field emission scanning electron microscopy, X-ray photoelectron spectroscopy and Photoluminescence spectroscopy techniques. The crystal structure, morphology, composition, and optical properties of these facile synthesized bismuth oxychloride nanoparticles (BiOCl NPs) were compared to those of traditional bismuth oxychloride. In addition, the photocatalytic performance of facile-synthesized BiOCl NPs and traditional BiOCl, as applied to the removal of hazardous organic dyes under visible light illumination, is thoroughly investigated. Our results reveal that facile-synthesized BiOCl NPs display strong UV-Vis light adsorption, improved charge carrier mobility and an inhibited rate of charge carrier recombination, when compared to traditional BiOCl. These enhancements result in an improved photocatalytic degradation rate of hazardous organic dyes under UV-Vis irradiance. For instance, the facile-synthesized BiOCl NPs attained 100% degradation of methylene blue and methyl orange dyes in approximately 30 mins under UV-Vis irradiation, against 55% degradation for traditional BiOCl under similar experimental conditions.

Recent advances in combretastatin based derivatives and prodrugs as antimitotic agents.

The dynamic and crucial role of tubulin in different cellular functions rendered it a promising target in anticancer drug development. Combretastatin A-4 (CA-4), an inhibitor of tubulin polymerization isolated from natural sources, is a lead molecule with significant cytotoxicity against tumour cells. Owing to its non polar nature it exhibits low solubility in natural biological fluids, thereby prompting the development of new CA-4 based derivatives. The modification of this lead molecule was mostly carried out by keeping the crucial cis-orientation of the double bond intact, along with a trimethoxyphenyl aromatic ring, by employing different approaches. The issue of solubility was also addressed by the development of water soluble prodrugs of CA-4. The present review highlights the investigations into the parallel development of both new CA-4 based derivatives and prodrugs in the past few years.

Heterodimerization at the dye sensitized TiO2 surface: an efficient strategy toward quick removal of water contaminants.

Sensitization of wide bandgap semiconductors with heterodimers for better solar light sensitivity has attracted widespread attention in the recent times. However, application of heterodimerization for removing soluble water pollutants from waste water is sparse in the literature. In the present study, we have utilized heterodimerization of a model pollutant methylene blue (MB) with a ruthenium based dye N719 for the removal of the pollutant. We have synthesized N719 functionalized carbonate doped TiO2 microspheres (doped MS) which act as a novel material for the detoxification of MB containing water by adsorbing at the surface and eventually killing by photoinduced reduction under visible light irradiation. The mechanism of surface adsorption and photoreduction of MB are explored using steady state and time resolved spectroscopy studies. We have fabricated two types of prototype devices (flow device and active filter) using the functionalized doped MS. Both the devices show excellent dye removal activity and recyclability. The present study would find relevance in the removal of soluble pollutants from waste water.

Carbonate Doping in TiO2 Microsphere: The Key Parameter Influencing Others for Efficient Dye Sensitized Solar Cell.

Four key parameters namely light trapping, density of light harvesting centre, photoinduced electron injection and electron transport without self-recombination are universally important across all kinds of solar cells. In the present study, we have considered the parameters in the context of a model Dye Sensitized Solar Cell (DSSC). Our experimental studies reveal that carbonate doping of TiO2 mesoporous microspheres (doped MS) makes positive influence to all the above mentioned key parameters responsible for the enhanced solar cell efficiency. A simple method has been employed to synthesize the doped MS for the photoanode of a N719 (ruthenium dye)-based DSSC. A detail electron microscopy has been used to characterize the change in morphology of the MS upon doping. The optical absorption spectrum of the doped MS reveals significant shift of TiO2 (compared to that of the MS without doping) towards maximum solar radiance (~500 nm) and the excellent scattering in the entire absorption band of the sensitizing dye (N719). Finally, and most importantly, for the first time we have demonstrated that the solar cells with doped MS offers better efficiency (7.6%) in light harvesting compared to MS without doping (5.2%) and also reveal minimum self recombination of photoelectrons in the redox chain.

Use of quadrupole time of flight mass spectrometry for the characterization of transformation products of the antibiotic sulfamethazine upon photocatalysis with Pd-doped ceria-ZnO nanocomposite.

The photocatalytic degradation of the antibiotic sulfamethazine under excitation at 365 nm of Pd-doped ceria-ZnO nanocomposite, titanium dioxide and iron(III) aqua complex was deeply studied from the analytical point of view. It reveals the formation of nine degradation products that were detected in their protonated forms using LC/electrospray ionization quadrupole time-of-flight MS in the positive mode. Their formation involves the hydroxyl radical, and their concentrations increased with irradiation time. Collision-induced dissociation tandem mass spectrometry associated with the accurate mass measurements was efficiently used for the elucidation of their chemical structures. None of these identified degradation products has been already reported in the literature. Three by-products result from the hydroxylation at the pyrimidine moiety as well as at the aromatic part, two of them arise from the scission of the pyrimidine group, and finally, three of them come from the scission of the sulfamide bridge. This points the evidence of studying the fate of these degradation products if their toxicity is demonstrated because they are clearly the result of the reaction of hydroxyl radical with the antibiotic sulfamethazine.

The efficient photocatalytic degradation of methyl tert-butyl ether under Pd/ZnO and visible light irradiation.

Methyl tert-butyl ether is a commonly used fuel oxygenate that is present in gasoline. It was introduced to eliminate the use of leaded gasoline and to improve the octane quality because it aids in the complete combustion of fuel by supplying oxygen during the combustion process. Over the past decade, the use of MTBE has increased tremendously worldwide. For obvious reasons relating to accidental spillage, MTBE started to appear as an environmental and human health threat because of its nonbiodegradable nature and carcinogenic potential, respectively. In this work, MTBE was degraded with the help of an advanced oxidation process through the use of zinc oxide as a photocatalyst in the presence of visible light. A mixture of 200 mg of zinc oxide in 350 mL of 50 ppm MTBE aqueous solution was irradiated with visible light for a given time. The complete degradation of MTBE was recorded, and approximately 99% photocatalytic degradation of 100 ppm MTBE solution was observed. Additionally, the photoactivity of 1% Pd-doped ZnO was tested under similar conditions to understand the effect of Pd doping on ZnO. Our results obtained under visible light irradiation are very promising, and they could be further explored for the degradation of several nondegradable environmental pollutants.

Impact of metal ions in porphyrin-based applied materials for visible-light photocatalysis: key information from ultrafast electronic spectroscopy.

Protoporphyrin IX-zinc oxide (PP-ZnO) nanohybrids have been synthesized for applications in photocatalytic devices. High-resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD), and steady-state infrared, absorption, and emission spectroscopies have been used to analyze the structural details and optical properties of these nanohybrids. Time-resolved fluorescence and transient absorption techniques have been applied to study the ultrafast dynamic events that are key to photocatalytic activities. The photocatalytic efficiency under visible-light irradiation in the presence of naturally abundant iron(III) and copper(II) ions has been found to be significantly retarded in the former case, but enhanced in the latter case. More importantly, femtosecond (fs) transient absorption data have clearly demonstrated that the residence of photoexcited electrons from the sensitizer PP in the centrally located iron moiety hinders ground-state bleach recovery of the sensitizer, affecting the overall photocatalytic rate of the nanohybrid. The presence of copper(II) ions, on the other hand, offers additional stability against photobleaching and eventually enhances the efficiency of photocatalysis. In addition, we have also explored the role of UV light in the efficiency of photocatalysis and have rationalized our observations from femtosecond- to picosecond-resolved studies.

The effect of loading palladium on zinc oxide on the photocatalytic degradation of methyl tert-butyl ether (MTBE) in water.

A series of heterogeneous catalysts was prepared by doping zinc oxide with different palladium loadings in the range of 0.5%-1.5%. The prepared catalysts were characterized by SEM, TEM and XRD. These catalysts were applied to study the degradation of Methyl tert-Butyl Ether (MTBE). An amount of 100 mg of each of these catalysts was added to an aqueous solution of 100 ppm of MTBE. The resulting mixtures were irradiated with UV light for a period of 5 h. A 99.7% removal of MTBE was achieved in the case of the zinc oxide photocatalyst particles doped with 1% Pd. The photoreaction was found to be a first-order one.

Preparation and characterization of Pd doped ceria-ZnO nanocomposite catalyst for methyl tert-butyl ether (MTBE) photodegradation.

A series of binary oxide catalysts (ceria-ZnO) were prepared and doped with different amounts of palladium in the range of 0.5%-1.5%. The prepared catalysts were characterized by SEM, TEM, XRD and XPS, as well as by N2 sorptiometry study. The XPS results confirmed the structure of the Pd CeO2-x-ZnO. The photocatalytic activity of these catalysts was evaluated for degradation of MTBE in water. These photocatalyst efficiently degrade a 100ppm aqueous solution of MTBE upon UV irradiation for 5h in the presence of 100mg of each of these photocatalysts. The removal of 99.6% of the MTBE was achieved with the ceria-ZnO catalyst doped with 1% Pd. In addition to the Pd loading, the N2 sorptiometry study introduced other factors that might affect the catalytic efficiency is the catalyst average pore sizes. The photoreaction was determined to be a first order reaction.