Distinct Mechanisms of Cytotoxicity in Novel Nitrogenous Heterocycles: Future Directions for a New Anti-Cancer Agent

Electron-rich, nitrogenous heteroaromatic compounds interact more with biological/cellular components than their non-nitrogenous counterparts. The strong intermolecular interactions with proteins, enzymes, and receptors confer significant biological and therapeutic properties to the imidazole derivatives, giving rise to a well-known and extensively used range of therapeutic drugs used for infections, inflammation, and cancer, to name a few. The current study investigates the anti-cancer properties of fourteen previously synthesized nitrogenous heterocycles, derivatives of imidazole and oxazolone, on a panel of cancer cell lines and, in addition, predicts the molecular interactions, pharmacokinetic and safety profiles of these compounds. Method: The MTT and CellTiter-Glo^® assays were used to screen the imidazole and oxazolone derivatives on six cancer cell lines: HL60, MDA-MB-321, KAIMRC1, KMIRC2, MCF-10A, and HCT8. Subsequently, in vitro tubulin staining and imaging were performed, and the level of apoptosis was measured using the Promega ApoTox-Glo^® triplex assay. Furthermore, several computational tools were utilized to investigate the pharmacokinetics and safety profile, including PASS Online, SEA Search, the QikProp tool, SwissADME, ProTox-II, and an in silico molecular docking study on tubulin to identify the critical molecular interactions. Results: In vitro analysis identified compounds 8 and 9 to possess the most significant potent cytotoxic activity on the HL60 and MDA-MB-231 cell lines, supported by PASS Online anti-cancer predictions with pa scores of 0.413 and 0.434, respectively. In addition, compound 9 induced caspase 3/7 dependent-apoptosis and interfered with tubulin polymerization in the MDA-MB-231 cell line, consistent with in silico docking results, identifying binding similarity to the native ligand colchicine. All the derivatives, including compounds 8 and 9, had acceptable pharmacokinetics; however, the safety profile was suboptimal for all the tested derivates except compound 4. Conclusion: The imidazole derivative compound 9 is a promising anti-cancer agent that switches on caspase-dependent apoptotic cell death and modulates microtubule function. Therefore, it could be a lead compound for further drug optimization and development.     

Physical Properties,Field Purity,and Quantum Phase for a Two-Level Atom in Photon-Added Coherent States for the Morse Potential

In this paper, we consider a two-level atom (TLA) interacting with a field mode, which is initially in the photon-added coherent state for the Morse potential (PACSMP). We investigate the dynamical behavior of quantum entropy, the geometric phase, and the Mandel parameter and discuss the statistical and nonclassical properties of the field with regards to its PACSMP through the evolution of the Mandel parameter. We examine the effects of the number of added photons, the initial-state setting, and the Morse-potential parameters. We establish the relationship between the field purity, nonclassical properties, and geometric phase of the system state during the time evolution. The results show that the numbers of added photons and CSMP strength have the potential to affect the time evolution of the field purity, the geometric phase, and the Mandel parameter. We explore some important physical phenomena such as sudden death and sudden birth of the nonlocal correlation between TLA and field systems.     

Structural and compositional mapping of a phase-separated Langmuir–Blodgett monolayer by X-ray photoelectron emission microscopy

The structure and composition of phase-separated Langmuir–Blodgett monolayer films comprised of mixtures of arachidic acid (C₁₉H₃₉COOH) and perfluorotetradecanoic acid (C₁₃F₂₇COOH) were characterized using a combination of X-ray photoelectron emission microscopy (X-PEEM), secondary electron emission microscopy (SEEM) and atomic force microscopy (AFM). X-PEEM provides high lateral spatial resolution and is directly sensitive to the elemental and chemical (functional group) composition of these ultrathin films through the chemical sensitivity of NEXAFS spectroscopy; AFM provides high-resolution imaging, both in terms of lateral and vertical (height) film topography. SEEM provides additional structural and electronic information through work function and electron scattering effects. The combination is used for chemical mapping of the phase-separated domains in the monolayer film. Our results directly confirm previous AFM measurements that suggested that the discontinuous domains are enriched in arachidic acid, whereas the surrounding continuous domain is a mixture of both arachidic acid and perfluorotetradecanoic acid.     

2-Substituted-3,7-dinitro-11-oxatricycloundec-9-ene: an approach towards the synthesis of Ergot alkaloids

A simple and versatile method for the preparation of various ergoline or secoergoline skeleton, using 2-substituted-3,7-dinitro-11-oxatricycloundec-9-ene as key intermediates, is described. The key step involves an IMDAF reaction with an excellent stereocontrol. This novel synthetic route provides new cycloadducts as useful scaffolds for Ergot alkaloids synthesis.     

Structural and compositional mapping of a phase-separated Langmuir-Blodgett monolayer by atomic force microscopy

The structure and composition of a phase-separated arachidic acid (C19H39COOH) (AA) and perfluorotetradecanoic acid (C13F27COOH) (PA) Langmuir-Blodgett monolayer film was characterized by several different types of atomic force microscopic measurements. At the liquid-air interface, surface pressure-area isotherms show that mixtures of the two acids follow the additivity rule expected from ideal mixtures. Topographic images of the deposited monolayer indicate that the surfactants are oriented normal to the substrate surface, and that the acids undergo phase separation to form a series of discontinuous, hexagonal domains separated by a continuous domain. A combination of lateral force (friction) imaging and adhesion force measurements show that the discontinuous domains are enriched in AA, whereas the surrounding continuous domain is a mixture of both AA and PA. This was further verified by selective, in situ dissolution of AA by n-hexadecane, followed by high-resolution topographical imaging of the discontinuous domains.     

Mechanistic insight into domain formation and growth in a phase-separated Langmuir-Blodgett monolayer

The mechanism of the formation and growth of phase-separated domains in mixed arachidic acid (C19H39COOH) (AA) and perfluorotetradecanoic acid (C13F27COOH) (PA) monolayer films was investigated through a combination of surface pressure-area isotherm measurements and atomic force microscope (AFM) imaging. In the mixed AA-PA monolayer system, distinct discontinuous domains consisting primarily of AA form spontaneously in a surrounding continuous matrix enriched in PA. By varying the monolayer deposition conditions, including temperature, surface pressure, and the mechanical agitation of sample solutions, it was determined that phase-separated nuclei are formed initially in the bulk sample solution and further growth of domains proceeds on the subphase surface via an Ostwald ripening process involving the diffusion of AA from the matrix to the discontinuous domains. In addition, selective dissolution of the arachidic acid followed by in situ AFM imaging has allowed the visualization of the fusion of AA to the phase-separated domains and has highlighted some unusual pattern formation that occurs at low subphase temperatures.     

On M-functions and operator theory for non-self-adjoint discrete Hamiltonian systems

We study discrete, generally non-self-adjoint Hamiltonian systems, defining Weyl–Sims sets, which replace the classical Weyl circles, and a matrix-valued M-function on suitable cone-shaped domains in the complex plane. Furthermore, we characterise realisations of the corresponding differential operator and its adjoint, and construct their resolvents.     

Characterization of domain growth kinetics in a mixed perfluorocarbon-hydrocarbon Langmuir-Blodgett monolayer

The rate of domain growth in phase-separated, mixed Langmuir-Blodgett (LB) monolayers of arachidic acid, C(19)H(39)COOH (AA) and perfluorotetradecanoic acid, C(13)F(27)COOH (PA) was tracked via atomic force microscope measurements. The growth rate of domains comprised of phase-separated AA was consistent with that predicted by the Lifshitz-Slyozov model for diffusion-limited Ostwald ripening. In addition to Ostwald ripening, some evidence for domain coalescence was also observed when LB films were deposited under conditions of low temperature and short incubation times, though this tendency disappeared at higher deposition temperatures.     

Fluorescence Quantum Yield Determination of Propylparaben Using Flow Injection Spectroscopy

The determination of the fluorescence quantum yield of Propylparaben is introduced and applied to L-tyrosine as a standard by a new approach that can be applied to the pharmaceutical compound utilised in this study. The quantum yield is a critical figure of quality for the optical nature of a fluorophore. Numerous investigations have considered the glitter in both pharmaceutical and nature compounds for its medical and industrial significance. A straightforward method is detailed here to decide the quantum yield of Propylparaben in solution as an element of the fluorescence concentration. For this reason, L-Tyrosine is chosen as a fluorescence standard perspective to gauge the Propylparaben fluorescence quantum yield. The impacts of pH, solvents and flow rate on the assessment of quantum yield and quantum efficiency, for the reference and the solutions of Propylparaben, have been investigated. The results indicated that these parameters significantly influence the accuracy of the method. Diverse methods are concentrated on to represent distinctive quantum yield advancements with the quantum efficiency. The impact of these parameters was likewise considered. In this study, the application of the single method may be taken into consideration to compute quantum yield of Propylparaben, which was 0.36, and this is an exceptionally basic and general technique to solve the imperative issue of luminescence quantum yield assurance of other fluorescence compounds.     

In Vitro Phytochemical Screening,Cytotoxicity Studies of Curcuma longa Extracts with Isolation and Characterisation of Their Isolated Compounds

The Curcuma longa plant is endowed with multiple traditional and therapeutic utilities and is here explored for its phytochemical constituents and cytotoxic potential. Turmeric rhizomes were extracted from three different solvents and screened for the presence of different phytochemical constituents, observation of which indicated that the polar solvents favoured extraction of greater versatile phytochemical constituents. These extracts were investigated for their cytotoxic potential by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on three different of cell lines including SCC-29B (oral cancer cell line), DU-145 (prostate cancer cell line) and the Vero cell line (healthy cell line/non-cancerous cell line). This assay was performed by taking three extracts from isolated curcuminoids and a pure bioactive compound bisdemethoxycurcumin (BD). Bisdemethoxycurcumin was isolated from curcuminoids and purified by column and thin-layer chromatography, and its structural characterisation was performed with different spectroscopic techniques such as FTIR, NMR (¹H Proton and ¹³C Carbon-NMR) and LC-MS. Amongst the extracts, the ethanolic extracts exhibited stronger cytotoxic potential against the oral cancer cell line (SCC-29B) with an IC₅₀value of 11.27 μg/mL, and that this was too low of a cytotoxicity against the Vero cell line. Although, curcuminoids have also shown a comparable cytotoxic potential against SCC-29B (IC₅₀ value 16.79 μg/mL), it was not as potent against the ethanolic extract, and it was even found to be cytotoxic against healthy cell lines at a very low dose. While considering the isolated compound, bisdemethoxycurcumin, it also possessed a cytotoxic potential against the prostate cancer cell line (DU-145) (IC₅₀ value of 93.28 μg/mL), but was quite safe for the healthy cell line in comparison to doxorubicin.