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More efficient and preferably more convenient and greener synthetic solutions in coumarin scaffold functionalization are in steady demand. The Duff ortho-formylation of unsubstituted umbelliferone was revised in this study. The reaction conditions were optimized based upon data from the literature analysis and resulted in unexpectedly rapid ortho-formylation of umbelliferone, yielding a mixture of ortho-formyl position isomers. Thorough studies on the separation of ortho-formylated umbelliferones using chromatographic and recrystallization methods as well as the evaluation of their solubility in common organic solvents led to complete resolution of 8-formyl- and 6-formylumbelliferones. The precise protocol for simultaneous preparation, extraction, and purification of 8-formyl- and 6-formylumbelliferones is provided, and the prospective studies of biological and pharmacological activities of these compounds are synopsized.

Reactions of picolinamides with 1,3-propanesultone in methanol followed by the treatment with ketones led to a series of previously unknown chemical transformations, yielding first pyridinium salts (2a–f), with a protonated endocyclic nitrogen atom, and then heterocyclic salts (3a–j) containing an imidazolidin-4-one ring. The structures of intermediate and final products were determined by IR and 1H, 13C NMR spectroscopy, and X-ray study. The effects of the ketone and alcohol structures on the product yield were studied by quantum-chemical calculations. The stability of salts 3a–j towards hydrolysis and alcoholysis makes them excellent candidates for the search for new types of biologically active compounds.

Photo-controlled or photo-regulated molecules, especially biologically active and operating in physiological conditions, are in steady demand. Herein, furocoumaric and furocoumarinic acids being (Z/E)-isomers relative to each other were obtained in two stages starting from psoralen: the alkaline solvolysis of psoralen led to furocoumaric acid, which was further Z → E photoisomerized (365 nm) to furocoumarinic acid. The kinetics of Z → E photoisomerization was monitored by HPLC and UV-vis spectrophotometry. Photophysical characteristics in the aqueous phase for both acids, as well as the reversibility of (Z/E) photoisomerization process, were also assessed. Furocoumarinic acid was found to be visibly fluorescent at pH 2.0–12.0, with the maxima of fluorescence emission spectra being pH-dependent. The reverse E → Z photoisomerization predicted by quantum chemistry calculations as energetically favorable for the monoanionic form of furocoumarinic acid was proved in the experiment while being complicated by pyrone ring closure back to psoralen in acidic and neutral conditions. The preparative synthesis of furocoumarinic acid outlined in this work is particularly valuable in view of a wide range of pharmacological effects previously predicted for this compound.

We performed an in silico, in vitro, and in vivo assessment of a potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (compound 1) as a potential prodrug for cognitive function improvement in ischemic brain injury. Using in silico methods, we predicted the pharmacological efficacy and possible safety in rat models. In addition, in silico data showed neuroprotective features of compound 1, which were further supported by in vitro experiments in a glutamate excitotoxicity-induced model in newborn rat cortical neuron cultures. Next, we checked whether compound 1 is capable of crossing the blood–brain barrier in intact and ischemic animals. Compound 1 improved animal behavior both in intact and ischemic rats and, even though the concentration in intact brains was low, we still observed a significant anxiety reduction and activity escalation. We used molecular docking and molecular dynamics to support our hypothesis that compound 1 could affect the AMPA receptor function. In a rat model of acute focal cerebral ischemia, we studied the effects of compound 1 on the behavior and neurological deficit. An in vivo experiment demonstrated that compound 1 significantly reduced the neurological deficit and improved neurological symptom regression, exploratory behavior, and anxiety. Thus, here, for the first time, we show that compound 1 can be considered as an agent for restoring cognitive functions.

The synthesis of the products of the 1,3-propanesultone ring opening during its interaction with amides of pyridinecarboxylic acids has been carried out. The dependence of the yield of the reaction products on the position (ortho-, meta-, para-) of the substituent in the heteroaromatic fragment and temperature condition was revealed. In contrast to the meta- and para-substituted substrates, the reaction involving ortho-derivatives at the boiling point of methanol unexpectedly led to the formation of a salt. On the basis of spectroscopic, X-Ray, and quantum-chemical calculation data, a model of the transition-state, as well as a mechanism for this alkylation reaction of pyridine carboxamides with sultone were proposed in order to explain the higher yields obtained with the nicotinamide and its N-methyl analog compared to ortho or meta parents. Based on the analysis of ESP maps, the positions of the binding sites of reagents with a potential complexing agent in space were determined. The in silico evaluation of possible biological activity showed that the synthetized compounds revealed some promising pharmacological effects and low acute toxicity.

Hexacoordinated heteroligand silicon catecholates, although being prospective as easily soluble compounds with high hydrolytic stability and diverse redox properties, have been insufficiently studied. The transesterification of 1-(trimethoxysilylmethyl)-2-oxohexahydroaze or N-methyl-N-(trimethoxysilylmethyl)acetamide by two equivalents of catechol derivatives in the presence of dicyclohexylamine afforded a series of target compounds in good yield. The complexes were characterized using elemental analysis, FTIR, 1H, 13C and 29Si NMR spectra, X-ray crystallography and cyclic voltammetry. X-ray diffraction confirmed that the silicon atom possesses the octahedral geometry of the SiCO5 polyhedron that remains unchanged in solution as it follows from 29Si NMR data. The compounds demonstrated up to three oxidation waves; and the reduction profile strongly depended on the nature of the substituents on a catecholate anion.

Ischemic stroke triggers a whole cascade of pathological changes in the brain, one of which is postischemic inflammation. Since in such cases thrombolytic therapy is often not possible, methods that modulate inflammation and affect microglia become particularly interesting. We synthesized 3-(2-oxo-4-phenylpyrrolidin-1-yl)propane-1-sulfonate calcium(II) (Compound 4) and studied its anti-inflammatory activity in in vitro and in vivo models of inflammation and ischemia. Macrophage cell line RAW 264.7 was treated with lipopolysaccharides (LPS) and Compound 4 at various dosages to study the cytokine profile using real-time PCR and cytometric bead array (CBA). Stroke in rats was simulated by the middle cerebral artery occlusion method (MCAO). Several tests were performed to characterize the neurological deficit and locomotor activity of the rats, and afterwards, postmortem, the number of astrocytes was counted using immunohistochemistry. Compound 4 in in vitro tests dose-dependently reduced the expression of interleukin-1β (IL1β), and inducible nitric oxide synthase (iNOS) genes in cell culture and increased the concentration of cytokines: interleukin-2, 4, 6 (IL-2, IL-4, and IL-6). In vivo Compound 4 increased the orienting-exploratory behavior, and reduced neurological and motor deficit. The number of astrocytes that promote and support inflammation was lower in the group treated with Compound 4. The stroke volume measured by magnetic resonance imaging (MRI) showed no difference. We have shown that Compound 4 demonstrates anti-inflammatory activity by increasing the synthesis of anti-inflammatory and reducing pro-inflammatory cytokines, and positively affects the neurological deficit in rats. Thus, Compound 4 has a high therapeutic potential in the management of patients after a stroke and requires further study of its neuroprotective properties.

Autoluminescent plants engineered to express a bacterial bioluminescence gene cluster in plastids have not been widely adopted because of low light output. We engineered tobacco plants with a fungal bioluminescence system that converts caffeic acid (present in all plants) into luciferin and report self-sustained luminescence that is visible to the naked eye. Our findings could underpin development of a suite of imaging tools for plants. Luminescence is engineered in whole plants, without an exogenous substrate, using a fungal gene cluster.

Short-chain fatty acids (SCFAs) are microbial metabolites involved in immune regulation, energy metabolism, and intestinal barrier integrity. Among them, the role of hexanoic acid (C6), predominantly derived from dietary sources, remains poorly understood in chronic heart failure (CHF) and sarcopenia. A total of 636 patients with confirmed CHF were screened between 2019 and 2021. Sarcopenia was diagnosed in 114 patients, with 74 meeting the inclusion criteria for analysis. Plasma levels of SCFAs—including butanoic, propanoic, isobutyric, 2- and 3-methylbutanoic, hexanoic, pentanoic, and 4-methylpentanoic acids—were measured using HPLC-MS/MS. Muscle strength, mass, and physical performance were assessed using handgrip dynamometry, bioelectrical impedance analysis, and SPPB, respectively. All patients showed elevated SCFA levels compared to reference values. Butanoic acid levels exceeded reference values by 32.8-fold, propanoic acid by 10.9-fold, and hexanoic acid by 1.09-fold. Patients with plasma hexanoic acid levels above the 50th percentile had a seven-fold increased mortality risk (OR = 7.10; 95% CI: 1.74–28.9; p < 0.01). Kaplan–Meier analysis confirmed significantly lower survival in this group (p = 0.00051). The mean left ventricular ejection fraction was 41.2 ± 7.5%, and the mean SPPB score was 6.1 ± 1.8, indicating impaired physical performance. Elevated plasma hexanoic acid is associated with poor prognosis in CHF patients with sarcopenia. These findings suggest that C6 may serve as a potential prognostic biomarker and therapeutic target in this population.

This study investigates the therapeutic potential of a new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner’s chronic unpredictable mild stress model of male Wistar rats was used as a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group with saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light–dark box, were used to assess the animals’ conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to the intact animals. These results suggest that Compound I has reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.