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The synthesized compound, 1-(2-ethoxyethyl)-4-(pent-1-yn-1-yl)piperidin-4-yl propionate (EPPP), and its 1:1 complex with β-cyclodextrin (EPPPβCD) have been characterized for the first time through a comprehensive suite of analytical methods. This study explores the therapeutic potential of EPPPβCD in modulating immune responses and accelerating the resolution of septic inflammation induced by chromium and vanadium ions in outbred male rats. The research highlights the significant impact of EPPPβCD on the dynamics of regulatory T lymphocytes (Tregs), notably causing a reduction in the CD4+CD25+ fractions at the onset of inflammation. This effect is attributed to the inhibition of Treg proliferation, which is crucial in hastening the resolution of inflammation. These findings underscore the potential of EPPPβCD as a promising therapeutic agent in controlling and mitigating inflammation mediated by heavy metal exposure, thereby offering a new avenue for the development of anti-inflammatory treatments.

Pain and anesthesia are a problem for all physicians. Scientists from different countries are constantly searching for new anesthetic agents and methods of general anesthesia. In anesthesiology, the role and importance of local anesthesia always remain topical. In the present work, a comparative analysis of the results of pharmacological studies on models of the conduction and terminal anesthesia, as well as acute toxicity studies of the inclusion complex of 1-methyl-4-ethynyl-4-hydroxypiperidine (MEP) with β-cyclodextrin, was carried out. A virtual screening and comparative analysis of pharmacological activity were also performed on a number of the prepared piperidine derivatives and their host–guest complexes of β-cyclodextrin to identify the structure–activity relationship. Various programs were used to study biological activity in silico. For comparative analysis of chemical and pharmacological properties, data from previous works were used. For some piperidine derivatives, new dosage forms were prepared as beta-cyclodextrin host–guest complexes. Some compounds were recognized as promising local anesthetics. Pharmacological studies have shown that KFCD-7 is more active than reference drugs in terms of local anesthetic activity and acute toxicity but is less active than host–guest complexes, based on other piperidines. This fact is in good agreement with the predicted results of biological activity.

Abstract Forming complexes with β-cyclodextrin can enhance stability, dissolution rate, solubility, and bioavailability of an active pharmaceutical ingredient. In this study, the inclusion behavior between β-cyclodextrin (β-CD) and diphenhydramine, clonidine, and tolperisone in DMSO-d6 was investigated using NMR spectroscopy. 1H, 13C, COSY, HMQC, and ROESY data were applied to determine the structure of inclusion complexes, and molecular docking analysis was engaged to identify the most favorable host–guest interactions in the inclusion complexes. Complexation of β-CD with diphenhydramine, clonidine, and tolperisone is accompanied by the insertion of a molecular fragment of the guest molecule, one molecule of diphenhydramine and tolperisone, and two molecules of clonidine, into the inner sphere of one host molecule. The reported study provides useful information for the potential application of the complexation of β-CD with diphenhydramine, clonidine, and tolperisone. This may be a good strategy for the development of solid pharmaceutical dosage forms based on β-CDs as a drug delivery system. Article highlights The inclusion complexes of β-CD and diphenhydramine, clonidine, and tolperisone were synthesized and analyzed using 1Н, 13С, COSY, HMQC, and ROESY spectroscopy. Diphenhydramine, clonidine, and tolperisone interact with β-CD with the formation of stable 1:1 stoichiometric complexes for β-CD:diphenhydramine and β-CD:tolperisone, and 1:2 stoichiometric complex for β-CD:clonidine. Possible structures of the inclusion complexes between β-CD and diphenhydramine, clonidine, and tolperisone were determined using molecular docking in the software AutoDock 4.0.