Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies

Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.     

Iridoids Isolation from a Phytochemical Study of the Medicinal Plant Teucrium parviflorum Collected in Iraqi Kurdistan

Herbal medicines are still widely practiced in Kurdistan Region-Iraq, especially by people living in villages on mountainous regions. Among plants belonging to the genus Teucrium (family Lamiaceae), which are commonly employed in the Kurdish traditional medicine, we have analyzed, for the first time, the methanol and aqueous methanol extracts of T. parviflorum aerial parts. The plant is mainly used by Kurds to treat jaundice, liver disorders and stomachache. We aimed to determine the phytochemical profile of the extracts and the structures of the main components, so to provide a scientific rationale for the ancient use of the plant in the ethno-pharmacological field. TLC analysis of the two extracts on silica gel and reversed phase TLC plates, using different visualization systems, indicated similar contents and the presence of phenolics, flavonoids, terpenoids and sugars. The chlorophyll-free extracts exhibited weak/no antimicrobial activities against a panel of bacteria (MICs = 800–1600 µg/mL) and fungal strains (MICs ≥ 5 mg/mL). At the concentration of 600 µg/mL, the methanol extract showed moderate antiproliferative effects against A549 and MCF-7 cancer cell lines in the MTS assay. Moreover, both extracts exhibited a significant dose-dependent free radical scavenging action against the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (EC₅₀ = 62.11 and 44.25 μg/mL, respectively). In a phytochemical study, a high phenolic content (77.08 and 81.47 mg GAE/g dry extract, respectively) was found in both extracts by the Folin–Ciocalteu assay. Medium pressure liquid chromatographic (MPLC) separation of the methanol extract on a reversed phase cartridge eluted with a gradient of MeOH in H₂O, afforded two bioactive iridoid glucosides, harpagide (1) and 8-O-acetylharpagide (2). The structures of 1 and 2 were established by spectral data, chemical reactions, and comparison with the literature. Interestingly, significant amounts of hepatotoxic furano neo-clerodane diterpenoids, commonly occurring in Teucrium species, were not detected in the extract. The wide range of biological activities reported in the literature for compounds 1 and 2 and the significant antiradical effects of the extracts give scientific support to the traditional use in Iraqi Kurdistan of T. parviflorum aerial parts for the preparation of herbal remedies.     

Solvation in mixed aqueous solvents from a thermodynamic cycle approach

A novel approach is presented for interpreting and potentially predicting values of the isothermal, isobaric transfer free energy, entropy, and enthalpy (Deltamicrotr2, Deltastr2, and Deltahtr2) for a solute between water and water-cosolvent mixtures. The approach explicitly accounts for volumetric properties of the solvent and solute (the equation of state, EoS) and casts the overall transfer process as a thermodynamic cycle with two stages: (1) isothermal solvent exchange from pure water to the cosolvent composition of interest at fixed mass density; (2) isothermal expansion or compression at the final solvent composition to recover the pressure of the initial state. Using molecular simulations with methane as the solute, the analysis is illustrated over a wide range of cosolvent concentrations for sorbitol-, ethanol-, and methanol-water binary mixtures. The EoS contribution semiquantitatively or quantitatively captures Deltamicrotr2, Deltastr2, and Deltahtr2 in almost all cases tested, highlighting the importance of considering the effects of changes in solvent density on the overall transfer process. The results also indicate that apolar solvation at these length scales is dominated by the work of cavity formation across a range of cosolvent species and concentrations.     

A new synthesis of lysophosphatidylcholines and related derivatives. Use of p-toluenesulfonate for hydroxyl group protection

A new stereoselective synthesis of lysophosphatidylcholines is reported. The synthesis is based upon (1) the use of 3-p-toluenesulfonyl-sn-glycerol to provide the stereocenter for construction of the optically active lysophospholipid molecule, (2) tetrahydropyranylation of the secondary alcohol function to achieve orthogonal protection of the sn-2- and sn-3-glycerol positions, and (3) elaboration of the phosphodiester headgroup using a 2-chloro-1,3,2-dioxaphospholane/trimethylamine sequence. In the course of developing the synthesis it has been discovered that methoxyacetate displacement of the sn-3-p-toluenesulfonate yields a reactive methoxyacetyl ester, which in turn can be selectively cleaved with methanol/tert-butylamine, while the ester group at the sn-1-position remains unaffected. The sequence has been shown to be suitable for preparation of spectroscopically labeled lysophosphatidylcholines. One of these compounds was readily converted to a double-labeled mixed-chain phosphatidylcholine applicable for real-time fluorescence resonance energy transfer (FRET) assay of lipolytic enzymes. In addition, the work led to new synthetic strategies based on chemoselective manipulation of the tosyl group in the presence of other base-labile groups such as FMOC derivatives that are often used for the protection of amino and hydroxyl groups in syntheses.     

Optimization and Validation of RP-LC/UV–VIS Detection Method for Simultaneous Determination of Fat-Soluble Anti-Oxidant Vitamins, all-trans-Retinol and α-Tocopherol in Human Serum: Effect of Experimental Parameters

A versatile isocratic reversed-phase liquid chromatographic/ultraviolet–visible detection method for simultaneous determination of all-trans-retinol and α-tocopherol in human serum was developed and validated after optimization of various chromatographic conditions and other experimental parameters. Analytes were separated on a Kromasil 100 RP₁₈ (150 × 4.6 mm, 5 μm) analytical column protected by a Perkin Elmer RP₁₈ (30 × 4.6 mm, 10 μm) guard cartridge. The mobile phase, methanol–water (96:04 v/v) was pumped at a flow rate of 2.2 mL min^?1 and the column eluents were monitored at the wavelength of 292 nm using retinyl acetate (1.0 μg mL^?1) as the internal standard for both analytes. Sample preparation was based on protein precipitation and stabilization with 2,6-bis(1,1-dimethylethyl)-4-methylphenol/ethanol and a two step extraction process using n-hexane followed by dichloromethane as extraction solvents. Sample size was kept 20 μL and separation of analytes was achieved in less than 7 min. The present method demonstrated acceptable values for specificity/selectivity, linearity within the expected concentration range, recovery, precision, sensitivity, stability of solutions, robustness, and system suitability specifications and tests. The method was used for monitoring all-trans-retinol and α-tocopherol concentrations in human serum samples and could also be applied to other sample matrices such as brain slices and cosmetic products if attention is paid to the extraction procedure.     

Phorbol Esters from Jatropha Meal Triggered Apoptosis, Activated PKC-δ, Caspase-3 Proteins and Down-Regulated the Proto-Oncogenes in MCF-7 and HeLa Cancer Cell Lines

Jatropha meal produced from the kernel of Jatropha curcas Linn. grown in Malaysia contains phorbol esters (PEs). The potential benefits of PEs present in the meal as anticancer agent are still not well understood. Hence, this study was conducted to evaluate the cytotoxic effects and mode of actions of PEs isolated from Jatropha meal against breast (MCF-7) and cervical (HeLa) cancer cell lines. Isolated PEs inhibited cells proliferation in a dose-dependent manner of both MCF-7 and HeLa cell lines with the IC₅₀ of 128.6 ± 2.51 and 133.0 ± 1.96 μg PMA equivalents/mL respectively, while the values for the phorbol 12-myristate 13-acetate (PMA) as positive control were 114.7 ± 1.73 and 119.6 ± 3.73 μg/mL, respectively. Microscopic examination showed significant morphological changes that resemble apoptosis in both cell lines when treated with PEs and PMA at IC₅₀ concentration after 24 h. Flow cytometry analysis and DNA fragmentation results confirmed the apoptosis induction of PEs and PMA in both cell lines. The PEs isolated from Jatropha meal activated the PKC-δ and down-regulated the proto-oncogenes (c-Myc, c-Fos and c-Jun). These changes probably led to the activation of Caspase-3 protein and apoptosis cell death occurred in MCF-7 and HeLa cell lines upon 24 h treatment with PEs and PMA. Phorbol esters of Jatropha meal were found to be promising as an alternative to replace the chemotherapeutic drugs for cancer therapy.     

The role of C-H and C-C stretching modes in the intrinsic non-radiative decay of triplet states in a Pt-containing conjugated phenylene ethynylene

The intrinsic non-radiative decay (internal conversion) from the triplet excited state in phosphorescent dyes can be described by a multi-phonon emission process. Since non-radiative decay of triplet excitons can be a significant process in organic light-emitting diodes, a detailed understanding of this decay mechanism is important if the overall device efficiency is to be controlled. We compare a deuterated Pt(II)-containing phenylene ethynylene with its non-deuterated counterpart in order to investigate which phonon modes control to the non-radiative decay path. We observe that deuteration does not decrease the non-radiative decay rate. A Franck-Condon analysis of the phosphorescence spectra shows that the electronic excitation is coupled strongly to the breathing mode of the phenyl ring and the C≡C carbon stretching modes, while high-energy C-H or C-D stretching modes play an insignificant role. We, therefore, associate the internal conversion process with the carbon-carbon stretching vibrations.     

Decomposition behaviors of various crystalline celluloses as treated by semi-flow hot-compressed water

Various types of crystalline cellulose consisting of group I (cell I, III_I, IV_I) and group II (cell II, III_II, IV_II) prepared from cotton linter were adjusted for their degree of polymerization (DP) as starting materials. These celluloses were then treated by semi-flow hot-compressed water (HCW) at 230–270 °C/10 MPa/2–15 min to study their decomposition behaviors. The treatments performed resulted in residues of celluloses and water-soluble (WS) portions. Consequently, the crystallinity of the residues was found to remain the same, but the DP was reduced as the temperature increased. Additionally, X-ray diffractometry and Fourier transform-infrared analyses demonstrated that crystallographic changes occurred for residues of cell III_I, IV_I and III_II. Despite these changes, the overall results of the residues showed that group I has higher resistance to decomposing than group II. As for the WS portions, the yields of the hydrolyzed and degraded products were higher in group II than group I, indicating that group II is less resistant to decomposition by HCW treatment. Results for both the residues and WS portions are in agreement with each other, showing that the degree of difficulty of decomposition was higher in group I than group II. Therefore, the decomposition behaviors of the celluloses are due to differences in the crystalline forms.     

Characterization and deposition of various light-harvesting antenna complexes by electrospray atomization

Photosynthetic organisms have light-harvesting complexes that absorb and transfer energy efficiently to reaction centers. Light-harvesting complexes (LHCs) have received increased attention in order to understand the natural photosynthetic process and also to utilize their unique properties in fabricating efficient artificial and bio-hybrid devices to capture solar energy. In this work, LHCs with different architectures, sizes, and absorption spectra, such as chlorosomes, Fenna–Matthews–Olson (FMO) protein, LH2 complex, and phycobilisome have been characterized by an electrospray-scanning mobility particle-sizer system (ES-SMPS). The size measured by ES-SMPS for FMO, chlorosomes, LH2, and phycobilisome were 6.4, 23.3, 9.5, and 33.4?nm, respectively. These size measurements were compared with values measured by dynamic light scattering and those reported in the literature. These complexes were deposited onto a transparent substrate by electrospray deposition. Absorption and fluorescence spectra of the deposited LHCs were measured. It was observed that the LHCs have light absorption and fluorescence spectra similar to that in solution, demonstrating the viability of the process.