Plants belonging to the Rosa genus are known for their high content of bioactive molecules and broad spectrum of healing and cosmetic activities. Rosa platyacantha Schrenk is a wild-type species abundant in the mountainous regions of Kazakhstan. The phytochemical composition as well as the bioactivity of R. platyacantha extracts have not been fully investigated to date. In this study, various parts of R. platyacantha plant, collected in Almaty region, Kazakhstan, were used to prepare five hydroalcoholic extracts (R1–R5). The extracts were compared for the content of phytochemicals and selected biological activities, which are important for the potential cosmetic application of R. platyacantha. Extract R3, prepared from flower buds, showed the most significant antioxidant and tyrosinase inhibitory potential, decreasing the monophenolase and diphenolase activities of tyrosinase. Extract R3 showed also collagenase inhibitory activity and cytotoxicity against human melanoma cells A375, being less cytotoxic for noncancerous skin keratinocytes HaCaT. Analysis of fractions E and F, obtained from R3 extracts, revealed that quercetin, kaempferol, rutin, and their derivatives are more likely responsible for the tyrosinase inhibitory properties of R. platyacantha extracts.

The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Na_v1.4 and Na_v1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.

The persistent evolution of SARS-CoV-2 necessitates novel antiviral strategies. This study evaluated the anti-HIV prodrugs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for repurposing against SARS-CoV-2, assessing key pharmacological indices (CC₅₀, EC₅₀, cytostatic effect, and therapeutic window). In vitro screening in Vero E6 cells measured cytotoxicity (via CCK-8/MTT assays) and antiviral activity against Kazakh B.1 and Wuhan strains. TDF (50 µg/mL) reduced high viral loads (MOI 2) by ~2 log₁₀ (100% inhibition), with minimal cytotoxicity (≥75% viability). TAF achieved near-complete suppression (100% inhibition) at 50 µg/mL, exhibiting dose-dependent inhibition (68–100%) at lower viral loads (MOI 0.01). Both prodrugs showed enhanced antiviral activity with prolonged exposure (96 h). Synergy assessments demonstrated favourable combination indices (CI < 1). Electron microscopy confirmed virion integrity post-treatment. These findings highlight TDF and TAF as promising candidates against SARS-CoV-2, with particular potential for targeting lymphoid reservoirs—sites implicated in persistent viral reservoirs that may contribute to long COVID pathogenesis. Further clinical validation is warranted.

Piperidine derivatives are of interest to researchers considering piperidines as an effective scaffold for the synthesis of new compounds. The aim of this research was to investigate the acute toxicity and local anesthetic activity of new synthesized 4-(Naphthalen-1-yloxy)but-2-yn-1-yl)-containing piperidine derivatives. Acute toxicity tests were performed on outbred laboratory mice by subcutaneous injection of increasing concentrations of the test solutions. An initial investigation of local anesthetic activity during infiltration anesthesia was performed on guinea pigs using the Bulbring & Wajda animal model. An in-depth study of the efficacy of the most active compound was performed on a model of infiltration anesthesia of the rabbit’s abdominal wall by determining the threshold of nociception during electrical stimulation. Studied new piperidine derivatives are low-toxic substances, which are confirmed by the results of an acute toxicity study. At the stage of the primary study of local anesthetic activity during infiltration anesthesia on the experimental Bulbring and Wajda model, the LAS-251 compound showed the greatest activity, surpassing the reference drugs in terms of anesthesia index, duration of full anesthesia and total duration of action. At the stage of in-depth study, despite a longer latency period, LAS-251 has a local anesthetic effect longer than procaine and is slightly inferior to lidocaine. Results of present study are promising because complex 1-(4-(naphthalen-1-yloxy)but-2-yn-1-yl)-4-phenylpiperidine (LAS-251) with cyclodextrin showed high local anesthetic activity. This new piperidine derivative is future-oriented for prospective studies of other types of anesthesia, as a potential medicinal substance for therapeutic use in the future.

Psoriasis is a chronic immune-mediated inflammatory disease associated with dysregulation of T-cell responses and cytokine signaling. The aim of this study was to synthesize and structurally characterize a piperidine α-hydroxyphosphonate (OPP) and to comparatively evaluate the effects of OPP and the vivo-phosphorodiamidate morpholino oligomer (vPMO) in a preclinical model of imiquimod-induced psoriasis. OPP was synthesized by hydrophosphorylation of 1-(3-isopropoxypropyl)piperidin-4-one with dimethyl phosphite; its structure was confirmed by IR, NMR spectroscopy, and elemental analysis. Psoriasis was induced in rats by topical application of imiquimod (IMQ). The animals were randomly allocated into six groups: control (C), experimental psoriasis (Ps), vehicle-treated (Ps/V), glucocorticosteroid-treated (Ps/GCS), piperidine α-hydroxyphosphonate-treated (Ps/OPP), and vivo-phosphorodiamidate morpholino oligomer-treated (Ps/vPMO) groups. Clinical manifestations were assessed on Days 3, 5, and 7 using a modified Psoriasis Area and Severity Index (PASI). During the 7-day observation period, body weight and the modified Psoriasis Area and Severity Index (PASI) score were assessed on Days 3, 5, and 7. Histopathological changes were evaluated using hematoxylin and eosin (H&E) staining. On day 7, CD3⁺CD45R⁻, CD4⁺CD8⁻, and CD4⁺CD25⁺ T-cell subpopulations were determined by flow cytometry, while serum concentrations of IL-6, TNF-α, IL-10, TGF-β1, IL-17A, and IL-22 were measured using an enzyme-linked immunosorbent assay (ELISA). IMQ administration resulted in the progressive development of psoriasiform skin lesions characterized by hyperkeratosis, acanthosis, inflammatory infiltration of the dermis, body weight loss, decreased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, increased levels of IL-6, IL-17A, and IL-22, and reduced IL-10 levels. OPP treatment was associated with a reduction in the total PASI score and the severity of scaling, as well as decreased serum concentrations of IL-6, IL-17A, and IL-22 and an increased IL-10 concentration. In addition, OPP increased the number of CD4⁺CD8⁻ cells compared with the psoriasis group, whereas the number of CD4⁺CD25⁺ cells remained below the control level. In contrast, vPMO treatment exhibited a distinct response profile characterized by increased numbers of CD3⁺CD45R⁻ and CD4⁺CD8⁻ cells, decreased IL-17A and IL-22 levels, increased IL-10 levels, and a particularly pronounced increase in TGF-β1 while producing less pronounced changes in certain cutaneous manifestations. Overall, OPP was characterized by a more consistent pattern of clinical, histopathological, and immunological changes, whereas vPMO treatment predominantly resulted in more pronounced alterations in systemic immunological parameters. These findings indicate distinct patterns of biological effects of OPP and vPMO in the IMQ-induced psoriasiform skin lesion model and support further preclinical investigation of these compounds. However, the observed changes do not allow definitive conclusions to be drawn regarding the underlying molecular mechanisms or the involvement of specific cellular pathways and should be interpreted in light of the limited observation period, the restricted panel of cellular markers examined, the absence of certain experimental controls, and the lack of pharmacokinetic data.