Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.     

Bioactive Properties and Phenolic Compound Profiles of Turnip-Rooted,Plain-Leafed and Curly-Leafed Parsley Cultivars

Petroselinum crispum Mill., Fuss., is a culinary vegetable used as an aromatic herb that garnishes and flavours a great variety of dishes. In the present study, the chemical profiles and bioactivities of leaf samples from 25 cultivars (three types: plain- and curly-leafed and turnip-rooted) from this species were assessed. Seven phenolic compounds were identified in all the varieties, including apigenin and kaempherol derivates. Apigenin-O-pentoside-O-hexoside was the major compound in all the tested parsley types (20, 22 and 13 mg/g of extract, respectively) and responsible for its excellent antioxidant activity, also investigated in this study. Antimicrobial activities were also explored, and the results revealed a good bioactivity against specific tested pathogens, such as bacteria and fungi. In conclusion, the leaves of all the types of P. crispum are a good source of natural bioactive compounds that confer health benefits, and thus, they should be part of a balanced and diversified diet.     

Bergenia Genus: Traditional Uses,Phytochemistry and Pharmacology

Bergenia (Saxifragaceae) genus is native to central Asia and encompasses 32 known species. Among these, nine are of pharmacological relevance. In the Indian system of traditional medicine (Ayurveda), “Pashanabheda” (stone breaker) is an elite drug formulation obtained from the rhizomes of B. ligulata. Bergenia species also possess several other biological activities like diuretic, antidiabetic, antitussive, insecticidal, anti-inflammatory, antipyretic, anti-bradykinin, antiviral, antibacterial, antimalarial, hepatoprotective, antiulcer, anticancer, antioxidant, antiobesity, and adaptogenic. This review provides explicit information on the traditional uses, phytochemistry, and pharmacological significance of the genus Bergenia. The extant literature concerned was systematically collected from various databases, weblinks, blogs, books, and theses to select 174 references for detailed analysis. To date, 152 chemical constituents have been identified and characterized from the genus Bergenia that belong to the chemical classes of polyphenols, phenolic-glycosides, lactones, quinones, sterols, tannins, terpenes, and others. B. crassifolia alone possesses 104 bioactive compounds. Meticulous pharmacological and phytochemical studies on Bergenia species and its conservation could yield more reliable compounds and products of pharmacological significance for better healthcare.     

Saffron: Chemical Composition and Neuroprotective Activity

Crocus sativus L. belongs to the Iridaceae family and it is commonly known as saffron. The different cultures together with the geoclimatic characteristics of the territory determine a different chemical composition that characterizes the final product. This is why a complete knowledge of this product is fundamental, from which more than 150 chemical compounds have been extracted from, but only about one third of them have been identified. The chemical composition of saffron has been studied in relation to its efficacy in coping with neurodegenerative retinal diseases. Accordingly, experimental results provide evidence of a strict correlation between chemical composition and neuroprotective capacity. We found that saffron’s ability to cope with retinal neurodegeneration is related to: (1) the presence of specific crocins and (2) the contribution of other saffron components. We summarize previous evidence and provide original data showing that results obtained both “in vivo” and “in vitro” lead to the same conclusion.     

Synthesis,Characterization, and Antiproliferative Activity of Novel Chiral [QuinoxP*AuCl2]+ Complexes

Herein is reported the synthesis of two Au(III) complexes bearing the (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (R,R-QuinoxP*) or (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxaline (S,S-QuinoxP*) ligands. By reacting two stoichiometric equivalents of HAuCl₄.3H₂O to one equivalent of the corresponding QuinoxP* ligand, (R,R)-(–)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (1) and (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) were formed, respectively, in moderate yields. The structure of (S,S)-(+)-2,3-Bis(tert-butylmethylphosphino)quinoxalinedichlorogold(III) tetrachloroaurates(III) (2) was further confirmed by X-ray crystallography. The antiproliferative activities of the two compounds were evaluated in a panel of cell lines and exhibited promising results comparable to auranofin and cisplatin with IC₅₀ values between 1.08 and 4.83 µM. It is noteworthy that in comparison to other platinum and ruthenium enantiomeric complexes, the two enantiomers (1 and 2) do not exhibit different cytotoxic effects. The compounds exhibited stability in biologically relevant media over 48 h as well as inert reactivity to excess glutathione at 37 °C. These results demonstrate that the Au(III) atom, stabilized by the QuinoxP* ligand, can provide exciting compounds for novel anticancer drugs. These complexes provide a new scaffold to further develop a robust and diverse library of chiral phosphorus Au(III) complexes.     

Electrochemical Conversion of CO2 to Syngas with Controllable CO/H2 Ratios over Co and Ni Single‐Atom Catalysts

The electrochemical CO₂ reduction reaction (CO₂RR) to yield synthesis gas (syngas, CO and H₂) has been considered as a promising method to realize the net reduction in CO₂ emission. However, it is challenging to balance the CO₂RR activity and the CO/H₂ ratio. To address this issue, nitrogen‐doped carbon supported single‐atom catalysts are designed as electrocatalysts to produce syngas from CO₂RR. While Co and Ni single‐atom catalysts are selective in producing H₂ and CO, respectively, electrocatalysts containing both Co and Ni show a high syngas evolution (total current >74 mA cm^?2) with CO/H₂ ratios (0.23–2.26) that are suitable for typical downstream thermochemical reactions. Density functional theory calculations provide insights into the key intermediates on Co and Ni single‐atom configurations for the H₂ and CO evolution. The results present a useful case on how non‐precious transition metal species can maintain high CO₂RR activity with tunable CO/H₂ ratios.     

An Activatable AIEgen Probe for High‐Fidelity Monitoring of Overexpressed Tumor Enzyme Activity and Its Application to Surgical Tumor Excision

Monitoring fluctuations in enzyme overexpression facilitates early tumor detection and excision. An AIEgen probe (DQM‐ALP) for the imaging of alkaline phosphatase (ALP) activity was synthesized. The probe consists of a quinoline‐malononitrile (QM) core decorated with hydrophilic phosphate groups as ALP‐recognition units. The rapid liberation of DQM‐OH aggregates in the presence of ALP resulted in aggregation‐induced fluorescence. The up‐regulation of ALP expression in tumor cells was imaged using DQM‐ALP. The probe permeated into 3D cervical and liver tumor spheroids for imaging spatially heterogeneous ALP activity with high spatial resolution on a two‐photon microscopy platform, providing the fluorescence‐guided recognition of sub‐millimeter tumorigenesis. DQM‐ALP enabled differentiation between tumor and normal tissue ex vivo and in vivo, suggesting that the probe may serve as a powerful tool to assist surgeons during tumor resection.     

Evaluation of Redox Activity of Human Myocardium‐derived Mesenchymal Stem Cells by Scanning Electrochemical Microscopy

In this study the redox activity of human myocardium‐derived mesenchymal stem cells (hmMSC) were investigated by redox‐competition (RC‐SECM) and generation‐collection (GC‐SECM) modes of scanning electrochemical microscopy (SECM), using 2‐methylnaphthalene‐1,4‐dione (menadione, MD) as a redox mediator. The redox activity of human healthy and dilated hmMSCs was evaluated by measuring reduction of MD. Measurements were performed by approaching and retracting the UME from the surface of growing hmMSC cells. The current study shows that the RC‐SECM mode can be applied to investigate integrity of cell membranes, whereas the most promising results were observed by using the GC‐SECM mode and applying the Hill's equation for the calculation/fitting of dependencies of electrical current vs menadione concentration. The calculated apparent Michaelis constant (K_M) for the production of menadiol (MDH₂) in the pathological hmMSC cells was 14.4 folds higher compared to that of the healthy hmMSC revealing the lover redox activity of pathological cells. Moreover, the calculated Hill's coefficient n shows a negative cooperative binding between MD and healthy hmMSC and positive cooperative binding between MD and pathological hmMSC. It means that healthy hmMSC is of lower affinity to MD, which is also related to the better membrane integrity of healthy cells. Data of this study demonstrate that SECM can be applied to investigate intracellular redox and membrane changes ongoing in human dilated myocardium‐derived hmMSC in order to improve their functioning and further regenerative potential.     

Synthesis and biological evaluation of 2-substituted vinylgembisphosphonates against Plasmodium falciparum and Trypanosoma brucei

Abstract

A series of 2-substituted vinylidene-1,1-bisphosphonate esters and their acids were synthesized and tested in vitro for activity against Plasmodium falciparum and Trypanosoma brucei. For each compound, % parasite viability in treated wells was calculated relative to untreated controls for both P. falciparum and T. brucei. Fifty percentage inhibitory concentration (IC₅₀) was also determined for the compounds. Chloroquine and pentamidine were used as positive control drug standards for activity against P. falciparum and T. brucei, respectively. The esters had better antiparasitic activity compared to their corresponding acids. Some of the compounds reduced % parasite viability to as low as 24.3% for P. falciparum and down to 0.602% for T. brucei. Tetraethyl-2-(o-tolyl)-ethene-1,1-bisphosphonate (3b) recorded the best IC₅₀ against T. brucei which was 0.0345?µmol/mL.     

Evaluation of various biological activities of natural compounds by TLC/HPTLC

Abstract

Over the last years, thin layer chromatography (TLC) has become an increasingly important tool in the analysis of natural compounds, being used not only as a simple method of separation, identification, and quantitative determination of natural constituents, but also as a method for evaluating the potential applications of the separated compounds, different bioassays being compatible with TLC. This is due to the TLC advantages, of which could be mentioned: the possibility to simply, quickly, and flexibly analyze many samples in parallel, without the need for special steps of sample purification, obtaining visual results, and the possibility of multiple detections, all of these being achieved at very low costs. Considering these, the aim of this study is to give an overview on the application of TLC in evaluation of different biological activities of natural compounds, focusing on antioxidant, enzymatic, antimicrobial, and hormonal activities.