A sequential one-pot approach to the tetrasubstituted 2H-imidazole scaffolds has been developed from disubstituted alkynes and structurally diverse ketones. The reaction proceeds via a diketo intermediate generated from internal alkynes followed by the addition of ammonium acetate and a suitable ketone, affording a diverse range of 2H-imidazoles. Using air-moisture stable reaction conditions and inexpensive reagents, the transformation demonstrates a broad substrate scope and good functional group compatibility.
Despite the advances in cancer therapy and early detection, breast cancer remains a leading cause of cancer-related deaths among females worldwide. The aim of the current study was to investigate the antitumor activity of a novel compound, 4-(3,4,5-trimethoxyphenoxy)benzoic acid (TMPBA) and its mechanism of action, in breast cancer. Results indicated the relatively high sensitivity of human breast cancer cell-7 and MDA-468 cells towards TMPBA with IC50 values of 5.9 and 7.9 µM, respectively compared to hepatocarcinoma cell line Huh-7, hepatocarcinoma cell line HepG2, and cervical cancer cell line Hela cells. Mechanistically, TMPBA induced apoptotic cell death in MCF-7 cells as indicated by 4',6-diamidino-2-phenylindole (DAPI) nuclear staining, cell cycle analysis and the activation of caspase-3. Western blot analysis revealed the ability of TMPBA to target pathways mediated by mitogen-activated protein (MAP) kinases, 5' adenosine monophosphate-activated protein kinase (AMPK), and p53, of which the concerted action underlined its antitumor efficacy. In addition, TMPBA induced alteration of cyclin proteins’ expression and consequently modulated the cell cycle. Taken together, the current study underscores evidence that TMPBA induces apoptosis in breast cancer cells via the modulation of cyclins and p53 expression as well as the modulation of AMPK and mitogen-activated protein kinases (MAPK) signaling. These findings support TMPBA’s clinical promise as a potential candidate for breast cancer therapy.
Taiwan is expected to become a superaged society by 2026. Community pharmacies have recently joined Taiwan’s primary care system; they have great potential to provide professional healthcare services. This study examined whether the services provided by community pharmacists enhance medication adherence, enable the identification and solution of drug therapy problems, and are accepted by community residents. The Department of Public Health, Taoyuan City, collaborated with the Taoyuan Pharmacist Association over 11 months in 2018 in enabling pharmacists to dispense prescriptions and provide medication adherence consultations, cognitive services, and home and institutional medical care services. This study designed four satisfaction questionnaires to assess the feasibility and performance of these services. Regarding the services related to medication knowledge and adherence, 92.10% of the patients reported overall satisfaction, and all understanding and ability scores were improved in more than 95% of patients. The number of patients highly cooperative regarding their medication had risen from 14 to 234 after the intervention, and the number with low medication adherence had dropped from 533 to 33. More than 90% of respondents indicated that the institutional medical care services had significantly improved their medication knowledge and behaviors. The feasibility of the incorporation of integrated the public health services model into age-friendly pharmacies was confirmed by this study.