Purpose: The increase in drug prescription for the elderly raises the risk of the occurrence of potentially inappropriate medications (PIMs), thus increasing the incidence of drug-related problems. Likewise, potential prescribing omissions (PPOs) are also highly prevalent in the elderly. This study aimed at assessing the prevalence of PIMs in the elderly by using the EU (7)-PIM list, STOPP criteria version 2 and the Beers criteria version 2015, as well as the prevalence of PPOs by applying the START criteria version 2 in elderly nursing home residents and outpatients of the Eastern Central Region of Portugal. Patients and Methods: A descriptive cross-sectional study was carried out in a sample of 90 Portuguese elderly people. Age, gender, diagnoses and medication history were collected from the patients' clinical records. The prevalence of PIMs and PPOs was measured according to each of the criteria applied. Results: The patients' ages ranged from 65 to 103 years, with an average age of 84.15 years. In addition, the average number of medications prescribed was 7.6. The STOPP criteria identified 250 PIMs affecting 77 patients (85.5%), the EU(7)-PIM list detected 94 PIMs in 58 patients (64.4%) and the Beers criteria identified 69 PIMs in 51 patients (56.6%). Therefore, the STOPP criteria version 2 identified substantially more PIMs than the other two tools. Furthermore, by applying the START criteria 68 PPOs were detected in 52 patients (57.7%). Conclusion: A high prevalence of PIMs and PPOs was observed, suggesting the need to implement actions aimed at reducing the phenomenon and thus help to improve the quality of care provided in nursing homes. The variations in prevalence with the different tools suggest the need to carefully choose the tool for medication review in the elderly.

The recent advances in synthesis and in vitro bioactivity studies of steroidal oximes contributed to understand the potential interest of the introduction of this functional group in the steroidal nucleus in the development of anticancer molecules. Moreover, the cytotoxic/enzyme inhibitory activity usually depends on the position of the oxime group in different steroid scaffolds. However, despite the promising results, it is necessary to perform more in vitro and in vivo assays not only to better explore the mechanisms of action but also to confirm the potential effectiveness and safety of this interesting family of compounds in clinical practice.

A series of ∆ 9,11 -estrone derivatives with A-and D-ring modifications has been synthesized and evaluated as antiproliferative agents. The cytotoxicity was assessed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF) by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and a cell cycle distribution analysis was performed by flow cytometry. Some compounds exhibited relevant cytotoxicity, particularly ∆ 9,11 -estrone, which was the most active against HepaRG cells (IC 50 = 6.67 µM). Besides the relevance of the double bond in the C-ring, the presence of a 16E-benzylidene group increased the antiproliferative effect on MCF-7 and T47-D cells. Moreover, the introduction of iodine in positions 2 and 4 of estrone seemed to induce a selective cytotoxicity for HepaRG cells. Flow cytometry experiments evidenced a 34% reduction of HepaRG cell viability after treatment with ∆ 9,11 -estrone and a cell cycle arrest at the G 0 /G 1 phase. Estrogenic activity was also observed for this compound at 0.1 µM in T47-D cells, and molecular docking studies estimated a marked interaction between this compound and the estrogen receptor α.

10β-Hydroxyestra-1,4-diene-3,17-dione (HEDD) is a natural product described as having interesting biological activities. However, the antiproliferative properties of this quinol are barely studied. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed in six cell lines (MCF-7, T47-D, LNCaP, HepaRG, Caco-2 and NHDF).Additionally, an in vitro estrogenicity assay and a cell viability analysis together with in silico molecular docking studies were carried out in order to understand the potential mechanism of cytotoxicity. Computational predictions of its pharmacokinetic and toxicity properties were also performed. HEDD displayed cytotoxic activity, particularly against hormone-dependent cancer cells and the flow cytometry analysis revealed that HEDD markedly reduced the viability of hepatic cancer cells. The molecular docking studies suggested a strong affinity towards the estrogen receptor α and 17β-hydroxysteroid dehydrogenase type 1. Moreover, it was predicted that HEDD may have good oral bioavailability and a low maximum tolerated dose in humans.

The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G2/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.