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The growing number of cancer cases highlights the urgent need to develop new therapies based on effective molecules. Although anticancer activity remains a key element of oncological pharmacology, the importance of agents that support physiological functions and improve the quality of life of cancer patients is also recognised. Compounds that combine these two functions could represent a significant trend in oncology. Moreover, repurposing approved drugs for conditions beyond their original indications could be a promising strategy. An interesting example of this is synthetic flozins (SGLT2 inhibitors), which were originally designed and developed to treat type 2 diabetes mellitus. These compounds contain various aromatic and heteroaryl structures, and changes in these substituents affect the binding strength and therapeutic potency of SGLT2 inhibitors. Beyond their antidiabetic effects, SGLT2 inhibitors exert well-documented cardioprotective and nephroprotective actions, restoring metabolic homeostasis. Given these pleiotropic properties, they could benefit oncology by improving systemic functions and by directly influencing the invasion of cancer cells. This article provides an overview of the use of synthetic flozins in various contexts, with a particular focus on their potential impact on cancer biology and treatment, consolidating their position as multifunctional agents of growing systemic relevance.

A series of caffeic acid derivatives were synthesized via a modified Wittig reaction which is a very important tool in organic chemistry for the construction of unsaturated carbon–carbon bonds. All reactions were performed in water medium at 90 °C. The aqueous Wittig reaction worked best when one unprotected hydroxyl group was present in the phenyl ring. The olefinations in the aqueous conditions were also conducted with good yields in the presence of two unprotected hydroxyl groups. When the number of the hydroxyl groups was increased to three, the reaction yields were worse, and the derivatives 12, 13, and 18 were obtained with 74%, 37%, and 70% yields, respectively. Nevertheless, the Wittig reaction using water as the essential medium is an elegant one-pot synthesis and a greener method, which can be a safe alternative for implementation in organic chemistry. The obtained compounds were tested for their antioxidant activity, and 12, 13, and 18 showed the highest activities. Moreover, all synthesized compounds displayed no cytotoxicity, and can therefore be used in the pharmaceutical or cosmetic industry.

It has been known since the 1990s that the introduction of a ferrocenyl–type substituent into compounds with proven biological activity can improve their properties. More recently, it was also shown that a carbon bridge connecting the two cyclopentadienyl rings in ferrocene derivatives could enhance the biological properties of the new compounds compared to those without them. However, the synthesis of ferrocenes with this additional linker, known as ansa–ferrocenes, is more difficult due to advanced synthetic protocols and the phenomenon of planar chirality in ring–substituted compounds. As a result, research into the formation of hybrids, conjugates and other ansa–ferrocene derivatives has not been widely conducted. This review discusses the potential biological properties of these units, covering scientific articles published between 1980 and 2024.

We report the synthesis of 5,7-diiodoquinolin-8-yl ester of caffeic acid and its O,O-diallyl-protected analogue. The compounds from the hybrid class were fully characterised using NMR spectroscopy and high-resolution mass spectrometry.

A series of new uracil derivatives/ursolic acid hybrids were designed and synthesised as potential cytotoxic agents. The uracil, thymine, 6-methyluracil and 2-thiouracil moieties were linked to ursolic acid ( 1 ) through alkyl chains of different lengths (either four or six -CH 2 - units). The cytotoxic activity of the synthesised conjugates was determined using the hormone-dependent breast cancer cell line MCF–7, the triple-negative breast cancer (TNBC) cell line MDA-MB-231 and normal cell lines: human skin fibroblasts (CCD-25Sk) and human bronchial epithelium (BEAS-2B). The five compounds, 4a , 5a , 6a , 7a and 9a , exhibited a significant reduction in the cell viability of human BC cell lines. Analog 6a , which demonstrated high cytotoxic activity against MCF-7 and MDA-MB-231 cell lines with IC 50 values of 14.00 µM and 5.83 µM, respectively, was also antitumorigenic in all biochemical assays. It increased p53 and Bax levels in MDA-MB-231 cells as well as significantly decreased Akt kinase levels in the tested cells, and effectively inhibited collagen biosynthesis. Finally, for the selected compounds, we computationally predicted their ADME properties and performed molecular docking to Akt protein kinase. The results of computational docking indicated that the preferred binding mode for all of them was the inactive form of Akt kinase, as in the case with known Akt allosteric inhibitors.

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (1), 5,11-dimethyl-5H-indolo[2,3-b]quinolin (2), capecitabine (3), diosgenin (4), tigogenin (5), flumethasone (6), fluticasone propionate (7), ursolic acid methyl ester (8), and β-sitosterol (9) was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (1), and the derivatization of diosgenin (4), tigogenin (5), and capecitabine (3) resulted in obtaining different compounds from those designed. Nevertheless, in all above cases we were able to obtain thiol-containing derivatives of selected biological active compounds. Moreover, a modelling study for the two-step thiolation of genistein and some of its derivatives was accomplished using the density functional theory (B3LP). A hypothesis on a possible reason for the unsuccessful deprotection of the thiolated genistein is also presented based on the semiempirical (PM7) calculations. The developed methodology gives access to new sulphur derivatives, which might find a potential therapeutic benefit.

Acute myeloid leukemia (AML) is a malignant hematopoietic disease with poor prognosis for most patients. Conventional chemotherapy has been the standard treatment approach for AML in the past 40 years with limited success. Although, several targeted drugs were recently approved, their long-term impact on survival of patients with AML is yet to be determined. Thus, it is still necessary to develop alternative therapeutic approaches for this disease. We have previously shown a marked synergistic anti-leukemic effect of two polyphenols, curcumin (CUR) and carnosic acid (CA), on AML cells and . In this study, we identified another phenolic compound, methyl 4-hydroxycinnamate (MHC), which among several tested phytochemicals could uniquely cooperate with CA in killing AML cells, but not normal peripheral blood mononuclear cells. Notably, our data revealed striking phenotypical and mechanistic similarities in the apoptotic effects of MHC+CA and CUR+CA on AML cells. Yet, we show that MHC is a non-fluorescent molecule, which is an important technical advantage over CUR that can interfere in various fluorescence-based assays. Collectively, we demonstrated for the first time the antileukemic activity of MHC in combination with another phenolic compound. This type of synergistically acting combinations may represent prototypes for novel antileukemic therapy.

Background A phenomenon of simulator sickness is measurable in terms of physiological symptoms. The article presents the practical use of the Simulator Sickness Questionnaire (SSQ) in post-exposure research, together with feedback given by the examined drivers. Material and Methods The study was conducted on the AutoSim AS 1600 simulator, and involved 130 drivers attending preliminary and periodic qualification courses in road transportation. The following tools were used throughout the research: the SSQ by Kennedy et al., translated into Polish by Biernacki et al. (with symptoms including nausea, oculomotor disturbances & disorientation symptoms, and the SSQ total), and a tool evaluating the SSQ (comprehensibility and time consumption on a 1–6 scale). Results In the study group (N = 130), some statistically significant differences in the SSQ results were observed. Among younger drivers ( 29.5 years old) – the disorientation symptoms after simulation. The length of sleep and the quality assessment of the conducted task were higher in the asymptomatic groups. Also, the results indicate a positive reception of the tool by the examined individuals (N = 113), with time consumption marked as low (M = 2.44 on a 1–6 scale) and comprehensibility as high (M = 5.62 on a 1–6 scale). Conclusions The research indicates the occurrence of simulator sickness symptoms even in simulators, which accurately reflect vehicle movements. The feedback given by the examined individuals, together with the level of involvement in the SSQ use, indicates a positive reception of the tool. Med Pr. 2020;71(1):47–58

Introduction: This article discusses the correlation between sensory processing sensitivity (SPS) as a feature of personality and temperament and paramedics' subjective perception of noise inside an ambulance. Description of the theoretical basis of SPS has been strongly depicted. Materials and methods: Polish translation of SPS 12-item short scale and a survey concerning the subjective perception of noise inside an ambulance have been used in this research. Assessment of noise included its three sources: emergency vehicle siren, resistance of rolling tires and noise produced by diesel engines. 46 paramedics from mobile emergency care units working in Poznan and the Poznan's district have taken part in the research. Paramedics with higher SPS results were selected, creating a highly sensitive people (HSP) group. Results: When non-HSP people were compared to paramedics from the HSP group, an emergency signal was considered more burdensome for HSP paramedics. The intensity of noise generated by the vehicle's suspension elements and tires was significantly higher in cars more than 3 years old. Older paramedics (≥30 years old) evaluated the intensity as well as burdensomeness of noise generated by suspension's elements and tires, higher than the younger (<30 years old) ones. Conclusions: Both paramedics and drivers as occupational groups are liable to noise, which seems to be particularly harmful and burdensome to the HSP group. Further studies should be provided in this area. This may lead to an increase not only in their productivity but also in their quality of life.

Plant phenolic compounds have shown the ability to cooperate with one another at low doses in producing enhanced anticancer effects. This may overcome the limitations (e.g., poor bioavailability and high-dose toxicity) in developing these agents as cancer medicines. We have previously reported that the hydroxycinnamic acid derivative (HCAD) methyl-4-hydroxycinnamate and the phenolic diterpene carnosic acid (CA) can synergistically induce massive calcium-dependent apoptosis in acute myeloid leukemia (AML) at non-cytotoxic concentrations of each agent. Here, we explored the chemical nature of the synergy between HCADs and either CA, in inducing cytotoxicity, or the active metabolite of vitamin D (calcitriol), in enhancing the differentiation of AML cells. This was done by determining the structure–activity relationship of a series of hydroxycinnamic acids and their derivatives (methyl hydroxycinnamates and hydroxybenzylideneacetones) in combination with CA or calcitriol. The HCAD/CA synergy required the following critical structural elements of an HCAD molecule: (a) the para-hydroxyl on the phenolic ring, (b) the carbon C7–C8 double bond, and (c) the methyl-esterified carboxyl. Thus, the only HCADs capable of synergizing with CA were found to be methyl-4-hydroxycinnamate and methyl ferulate, which also most potently enhanced calcitriol-induced cell differentiation. Notably, the C7–C8 double bond was the major requirement for this HCAD/calcitriol cooperation. Our findings may contribute to the rational design of novel synergistically acting AML drugs based on prototype combinations of HCADs with other agents studied here.