1H-Pyrazolo[3,4-b]quinolines: Synthesis and Properties over 100 Years of Research

This paper summarises a little over 100 years of research on the synthesis and the photophysical and biological properties of 1H-pyrazolo[3,4-b]quinolines that was published in the years 1911–2021. The main methods of synthesis are described, which include Friedländer condensation, synthesis from anthranilic acid derivatives, multicomponent synthesis and others. The use of this class of compounds as potential fluorescent sensors and biologically active compounds is shown. This review intends to summarize the abovementioned aspects of 1H-pyrazolo[3,4-b]quinoline chemistry. Some of the results that are presented in this publication come from the laboratories of the authors of this review.     

Pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine Sulfonamides as Novel Potential Anticancer Agents: Cytotoxic and Genotoxic Activities In Vitro

In this paper, we present for the first time the evaluation of cytotoxicity and genotoxicity of de novo synthesized pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides MM129, MM130, and MM131 in human tumor cell lines: HeLa, HCT 116, PC-3, and BxPC-3. Cytotoxic and genotoxic properties of the tested compounds were estimated using the MTT assay, comet assay (alkaline and neutral version), and γ-H2AX immuno-staining. Examined sulfonamides exhibited strong anticancer properties towards tested cells in a very low concentration range (IC₅₀ = 0.17–1.15 μM) after 72 h exposure time. The results of the alkaline and neutral version of the comet assay following 24 h incubation of the cells with tested compounds demonstrated the capability of heterocycles to induce significant DNA damage in exposed cells. HCT 116 cells were the most sensitive to the genotoxic activity of novel tricyclic pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulfonamides in the neutral version of the comet assay. Immunocytochemical detection of γ-H2AX showed an increase in DNA DSBs level in the HCT 116 cell line, after 24 h incubation with all tested compounds, confirming the results obtained in the neutral comet assay. Among all investigated compounds, MM131 showed the strongest cytotoxic and genotoxic activity toward all tested cell types. In conclusion, our results suggest that MM129, MM130, and MM131 exhibit high cytotoxic and genotoxic potential in vitro, especially towards the colorectal cancer cell line HCT 116. However, further investigations and analyses are required for their future implementation in the field of medicine.     

Regiospecific Hydrogenation of Bromochalcone by Unconventional Yeast Strains

This research aimed to select yeast strains capable of the biotransformation of selected 2′-hydroxybromochalcones. Small-scale biotransformations were carried out using four substrates obtained by chemical synthesis (2′-hydroxy-2″-bromochalcone, 2′-hydroxy-3″-bromochalcone, 2′-hydroxy-4″-bromochalcone and 2′-hydroxy-5′-bromochalcone) and eight strains of non-conventional yeasts. Screening allowed for the determination of the substrate specificity of selected microorganisms and the selection of biocatalysts that carried out the hydrogenation of tested compounds in the most effective way. It was found that the position of the bromine atom has a crucial influence on the degree of substrate conversion by the tested yeast strains. As a result of the biotransformation of the 2′-hydroxybromochalcones, the corresponding 2′-hydroxybromodihydrochalcones were obtained. The products obtained belong to the group of compounds with high potential as precursors of sweet substances.     

Porphyrins as Chelating Agents for Molecular Imaging in Nuclear Medicine

Porphyrin ligands, showing a significant affinity for cancer cells, also have the ability to chelate metallic radioisotopes to form potential diagnostic radiopharmaceuticals. They can be applied in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) to evaluate metabolic changes in the human body for tumor diagnostics. The aim of this paper is to present a short overview of the main metallic radionuclides complexed by porphyrin ligands and used in these techniques. These chelation reactions are discussed in terms of the complexation conditions and kinetics and the complex stability.     

Photon Upconversion in Small Molecules

Upconversion (UC) is a process that describes the emission of shorter-wavelength light compared to that of the excitation source. Thus, UC is also referred to as anti-Stokes emission because the excitation wavelength is longer than the emission wavelength. UC materials are used in many fields, from electronics to medicine. The objective of using UC in medical research is to synthesize upconversion nanoparticles (UCNPs) composed of a lanthanide core with a coating of adsorbed dye that will generate fluorescence after excitation with near-infrared light to illuminate deep tissue. Emission occurs in the visible and UV range, and excitation mainly in the near-infrared spectrum. UC is observed for lanthanide ions due to the arrangement of their energy levels resulting from f-f electronic transitions. Organic compounds and transition metal ions are also able to form the UC process. Biocompatible UCNPs are designed to absorb infrared light and emit visible light in the UC process. Fluorescent dyes are adsorbed to UCNPs and employed in PDT to achieve deeper tissue effects upon irradiation with infrared light. Fluorescent UCNPs afford selectivity as they may be activated only by illumination of an area of diseased tissue, such as a tumor, with infrared light and are by themselves atoxic in the absence of infrared light. UCNP constructs can be monitored as to their location in the body and uptake by cancer cells, aiding in evaluation of exact doses required to treat the targeted cancer. In this paper, we review current research in UC studies and UCNP development.     

Polyphenols Content,Antioxidant Properties and Allergenic Potency of Organic and Conventional Blue Honeysuckle Berries

Blue honeysuckle berries are a rich source of polyphenols with strong antioxidant properties. The purpose of this research was to determine the effect of organic and conventional cultivation on the polyphenols, antioxidant and allergenic potency of blue honeysuckle berry cultivars: ‘No 30’, ‘Jolanta’ and ‘Indygo’ in two growing seasons. Identification of individual polyphenols was performed using the HPLC method; the total polyphenols content and antioxidant activity were determined by spectrophotometric methods. The determination of allergic potency was tested by ELISA. In the second year of the study the total polyphenols were significantly higher in organic blue honeysuckle than in the conventional blue honeysuckle. In both growing seasons, the ‘Indygo’ cv. was characterized by the highest concentration of all bioactive compounds 3241.9 mg and 3787.2 mg per 100 g⁻¹ D.W. A strong correlation was found between the polyphenol content and the antioxidant activity for organic fruit in both years, as well as for allergenic potency. Contrary to the best bioactive properties was ‘Indigo’ cv., with the highest allergenic potency (108.9 and 139.2 ng g⁻¹ D.W.). The lowest content of specific allergens was found in the ‘No 30’ cv. Since honeysuckle is still a new cultivated plant, information about its allergenic potency is insufficient.     

Computational Bioprospecting Guggulsterone against ADP Ribose Phosphatase of SARS-CoV-2

Coronavirus Disease-2019 (COVID-19) is a highly contagious disease caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) classified the disease a as global public health hazard on 11 March 2020. Currently, there are no adequate measures to combat viral infections, including COVID-19, and the medication guidelines for the management of COVID-19 are dependent on previous findings from SARS-CoV and MERS-CoV research. Natural products have achieved widespread acceptance around the world as a means of enhancing healthcare and disease prevention. Plants are a potential source of antiviral factors such as flavonoids, phenolic acids, terpenoids, and others. Some of these agents exhibit a broad spectrum of antiviral activity. This study aimed to screen herbal leads for possible inhibitors of the SARS-CoV-2 ADP Ribose Phosphatase enzyme (ARP). Guggulsterone was found to be highly stabilized within the active site of the viral ARP enzyme by molecular dynamic simulation with very little fluctuation throughout the simulation timeframe of 100 ns. Thus, guggulsterone can be further used to develop a safe and competent medication for evolving therapy against SARS-CoV-2 in post-preclinical and clinical trials.     

Enhanced Performance of Camphorsulfonic Acid-Doped Perovskite Solar Cells

High-quality perovskite film with large grains and therefore reduced grain boundaries plays a significant role in improving the power conversion efficiency (PCE) and ensuring good long-term stability of the perovskite solar cells. In this work, we found that adding camphorsulfonic acid (CSA), a Lewis base, to the perovskite solution results in the crystallization of larger perovskite grains. By varying the concentration of CSA, we found that the optimal concentration of the additive is 1 mg/mL, which leads to an 20% increase in PCE of the cells compared to the reference CSA-free cell. Interestingly, we observed that the PCE of cells with an excess of CSA was initially poor, but may increase significantly over time, possibly due to CSA migration to the hole-transporting layer, leading to an improvement in its conductivity.     

Photoinduced Processes in Rhenium(I) Terpyridine Complexes Bearing Remote Amine Groups: New Insights from Transient Absorption Spectroscopy

Photophysical properties of two Re(I) complexes [ReCl(CO)₃(R-C₆H₄-terpy-κ²N)] with remote amine groups, N-methyl-piperazinyl (1) and (2-cyanoethyl)methylamine (2), were investigated. The complexes show strong absorption in the visible region corresponding to metal-to-ligand charge transfer (¹MLCT) and intraligand-charge-transfer (¹ILCT) transitions. The energy levels of ³MLCT and ³ILCT excited-states, and thus photoluminescence properties of 1 and 2, were found to be strongly affected by the solvent polarity. Compared to the parent chromophore [ReCl(CO)₃(C₆H₅-terpy-κ²N)] (3), both designed complexes show significantly prolonged (by 1–2 orders of magnitude) phosphorescence lifetimes in acetonitrile and dimethylformamide, contrary to their lifetimes in less polar chloroform and tetrahydrofuran, which are comparable to those for 3. The femtosecond transient absorption (fsTA) measurements confirmed the interconversion between the ³MLCT and ³ILCT excited-states in polar solvents. In contrast, the emissive state of 1 and 2 in less polar environments is of predominant ³MLCT nature.