Polyazamacrocycles are currently being studied and used in a variety of applications beyond their traditional place in supramolecular and co-ordination chemistry. This study suggests additional applications of these compounds with particular emphasis on their use as antiproliferative agents that could be potentially used to treat cancer. Four polyazamacrocycles were tested in human prostate cancer LNCaP and prostate epithelial PNTA1 cells to analyze changes in cell proliferation and cell death capabilities. Their intracellular localization was also evaluated by confocal microscopy. The results show a decrease in proliferation rate and cell viability of LNCaP and PNTA1, after treatment with these compounds. The decrease in the number of viable cells is similar for the majority of the compounds studied, and at higher concentration, the proliferation efficiency decreased significantly in the cell lines studied. Also, our results suggest that L and L2 induce early apoptosis in PNTA1 cells and late apoptosis/necrosis in LNCaP cells. The compounds did not induce a significant increase in necrosis of both cell types. Although the compounds did not localize in a unique organelle, all of them have as main target the Golgi apparatus and other localization profiles differed depending on the cell line.

This work comprises the Internship Report and the Monography entitled "New Advances and Old Challenges in the Realm of Alzheimer's Disease," related to the Curricular Unit "Internship." The report describes the curricular internship conducted in Community Pharmacy at Farmácia Cruzeiro, from December 2023 to May 2024. The monography discusses current treatments, innovative treatments, and the challenges in treating Alzheimer’s Disease (AD).AD is a prevalent condition in today’s society, but its pathophysiology and underlying mechanisms remain unknown. This presents a significant challenge for the development of effective treatments. Despite significant advancements, current therapeutic approaches face considerable limitations. Often, treatments fail to provide sustained cognitive improvements, address the complexity of the pathology, or overcome challenges related to drug delivery.This monography covers conventional treatments targeting the key proteins associated with the pathology, tau and beta-amyloid, as well as innovative treatments, some still in clinical trials, that also target these proteins. Special attention is given to Macrocyclic Compounds (MCs), which have the potential to overcome various limitations of conventional therapies, such as drug delivery across the blood-brain barrier. These compounds have unique structural qualities, including the ability to interact specifically and stably with biological targets, high affinity for these targets, and the ability to encapsulate molecules and ions.The pursuit of new therapies is essential to improve patient outcomes and enhance the understanding of this pathology. Investment in innovative approaches and overcoming current limitations will advance us towards a future where AD can be better controlled or even prevented.

Macrocyclic monoacyl lathyrane derivatives bearing a benzoyl moiety were previously found to be strong ABCB1 modulators. To explore the effects of different substituents of the aromatic moiety, 14 new compounds (1.1-1.7, 1.10, and 2.1-2.4) were prepared from jolkinol D (1), obtained from Euphorbia piscatoria, and from jolkinodiol (2), its hydrolysis derivative. Compounds 1.8 and 1.9, having aliphatic moieties, were also obtained. The reversal of ABCB1-mediated MDR was evaluated through functional and chemosensitivity assays on the human ABCB1-gene-transfected L5178Y mouse T-lymphoma cell line. Structure-activity relationships showed that addition of electron-donating groups to the aromatic moiety improved the activity. The effects on the ATPase activity of the strongest modulator (1.3) and the inactive jolkinol D (1) were also investigated and compared. Moreover, in the chemosensitivity assay, most of the compounds interacted synergistically with doxorubicin. Compounds 1.1-1.10 and 2.1-2.4 were further assessed for their collateral sensitivity effect against the human cancer cells: EPG85-257 (gastric) and EPP85-181 (pancreatic), and the matching drug-selected cells EPG85-257RDB, EPG85-257RNOV, EPP85-181RDB, and EPP85-181RNOV. The most promising ones (1.8 and 1.10) along with compound 3, previously selected, were investigated as apoptosis inducers. The compounds were able to induce apoptosis through caspase-3 activation, with significant differences being observed between the parental and resistant cells. © 2017 The American Chemical Society and American Society of Pharmacognosy.