Current Chemical Biology - Volume 14, Issue 4, 2020

Tumor cell growth and survival are the outcomes of communication between tumor cells and tumor microenvironment (TME). In other words, tumor cell growth and survival are greatly affected by the interaction between adjacent cells and tumor cells. In this paper, we review the recent advances in studies of TME, including metabolic interplays between tumor cells and their non-malignant neighbors (peaceful interaction and autophagy), trades of signaling pathways (approach to most important ones; cytokine pathway, NF-kB pathway, intra-tumoral hypoxia, oxidative stress, and nitric oxide-depended pathways), miRNAs (as the regulatory molecules which are present in TME), and Tumor-associated Exosomes (TAEs). Characterization of TME bio-molecules, nutrient changes, and cellular and molecular interactions help to clarify the progression of cancer and find novel targets for the treatment of cancer.

Objective: To synthesize novel bispyrazole heterocyclic molecules may have important biological activities and thus can serve as good candidates for pharmaceutical applications. Methods: The bispyrazole derivatives 3a-m were prepared by the condensation reaction of substituted aromatic aldehydes with 1,3-diketo-N-phenylpyrazole by using Mg/Al-LDH as a heterogeneous catalyst under THF solvent at the refluxing temperature. Results: This protocol describes the synthesis of bioactive compounds under mild reaction conditions, with good yields, and easiness of the catalyst separation from the reaction mixture. Furthermore, a mechanistic study has been performed by using DFT calculations to explain the observed selectivity of the condensation reaction between aryl aldehyde and 1,3- diketo-N-phenylpyrazole via Knoevenagel reaction. The local electrophilicity/ nucleophilicity explains correctly the experimental finding. Conclusion: In summary, the pharmacologically interesting bis-pyrazole derivatives were synthesized through Mg/Al-LDH as a solid base catalyst, in THF as a solvent. The synthesized bioactive compounds containing the pyrazole ring may have important biological activities and thus can serve as good candidates for pharmaceutical applications. Therefore, the catalyst Mg/Al-LDH showed high catalytic activity. Besides, a series of bispyrazole molecules were synthesized with a good yield and easy separation of the catalyst by simple filtration. Moreover, DFT calculations and reactivity indexes were used to explain the selectivity of the condensation reaction between aryl benzaldehyde and 1,3-diketo-N-phenylpyrazole via Knoevenagel reaction, and the results were in good agreement with the experimental finding.

Background: The genus Capsicum contains various sweet and hot pepper varieties, including Capsicum annum L. The various species in this genus are used as herbs, vegetables, or medicines, and recent studies have shown that they are a rich source of bioactive compounds as well. Objective: In this study, our objective was to evaluate the antioxidant activity as well as the content of phenols (TPC), the content of flavonoids (TFC) and total condensed tannins (TCT) of ethanolic extracts of the fresh and dried sweet pepper Capsicum annuum L. Methods: The antioxidant activities of the extracts were examined using different biochemical assays, namely diphenylpicrylhydrazyl (DPPH), total antioxidant capacity (TAC) and ferric reducing power (FRAP). The total phenolic contents (TPC) were determined spectrophotometrically according to the Folin-Ciocalteu colorimetric method. Total flavonoid content was measured by the aluminum chloride colorimetric assay. High-performance liquid chromatography (HPLC) has been used to identify the phenolic compounds in ethanolic extracts. Results: The obtained results showed the presence of considerable amounts of total phenolic (757.3±3.5 mgGAE/100g), flavonoid (482.66±1.5 mgQE/100g) and Condensed Tannins (15.97±0.5 mg GAE/100g) content in dry red pepper extract. The use of HPLC has allowed the identification of Gallic Acid, Ascorbic Acid, Chlorogenic Acid, Caffeic Acid, Quercetin, Vanillin, and Rutin in pepper ethanolic extracts. Green and yellow dry peppers contain significant amounts of gallic acid exceeding (134.0 μg /mg). The fresh yellow and red peppers also contained significant amounts of Quercetin exceeding (109.3 μg/mg), the dry red pepper has the strongest antioxidant activity. Conclusion: In conclusion, these findings can be regarded as very promising and justify further study, including the identification of antioxidant components in pepper extracts. Our work constitutes a first step in the study of fresh and dry sweet pepper as a promising source of natural antioxidants.

Background: Sago palm is an important agricultural starch-producing crop in Malaysia. The trunk of sago palm is responsible for the the starch to reach maturity for harvesting after ten years. However, there are sago palms that fail to develop thier trunk after 17 years of being planted. This is known as a stressed “non-trunking” sago palm, which reduces the economic value of the palms. Objective: The study was initiated to compare the differences in metabolite expression between trunking and non-trunking sago palms and secondly to determine the potential metabolite- makers that are related to differential phenotypes of sago palms. Methods: Metabolites were extracted using various solvents and analysed using NMR spectroscopy and GC-MS spectrometry. Data obtained were subjected to principal component analysis. Results: The study determined differential metabolites expression in the leaf extracts of normal trunking sago palm compared to the non-trunking palms. Metabolite groups differently expressed between trunking and non-trunking sago palm are oils and waxes, haloalkanes, sulfite esters, phosphonates, phosphoric acid, thiophene ester, terpenes and tocopherols. GC-MS analysis of Jones & Kinghorn extraction method determined two sets of metabolite markers, explaining the differences in metabolites expression of trunking and nontrunking sago palms in ethyl acetate and methanol extract of 89.55% comprising sulfurous ester compounds and 87.04% comprising sulfurous ester, sulfurous acid and cyclohexylmethyl hexyl ester, respectively. Conclusion: Two sets of metabolite markers were expressed in the trunking and nontrunking sago palms. These metabolites can potentially be used as markers for identifying normal and stressed plants.

Background: To investigate dynamic live tissue organophosphorus nerve agent uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported the first-in-class fluorine-18 [¹⁸F] radiolabeled Positron Emission Tomography (PET) imaging tracer known as [¹⁸F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer has been initially studied in live rats with PET imaging. Objective: We sought to evaluate the PET tracer in vivo using a new dose formulation of saline, ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo tracer performance to previous data collected using a CH3CN:PBS formulation. Methods: A high molar activity [¹⁸F]tracer radiosynthesis was used. Doses were formulated as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6 h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data were compared. Results and Discussion: An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable doses for 6 h (>99%). Arterial blood included a tracer and a single metabolite. The ex vivo biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed tissue levels: heart and lung, highest; liver, moderate; and brain, lowest. Conclusion: Imaging and biodistribution data were highly correlated with expected radioactivity tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as compared to the established CH3CN:PBS formulation. Overall, we found that the i.v. dose formulation changed the in vivo profile of an organophosphorus PET tracer that is considered an important finding for future organophosphorus PET tracer studies.