Click Chemistry as an Efficient Toolbox for Coupling Sterically Hindered Molecular Systems to Obtain Advanced Materials for Nanomedicine.

Since its conceptualization, click chemistry in all its variants has proven to be a superior synthesis protocol, compared to conventional methods, for forming new covalent bonds under mild conditions, orthogonally, and with high yields. If a term like reactive resilience could be established, click reactions would be good examples, as they perform better under increasingly challenging conditions. Particularly, highly hindered couplings that perform poorly with conventional chemistry protocols-such as those used to conjugate biomacromolecules (e.

Click synthesis of dendronized malonates for the preparation of amphiphilic dendro[60]fullerenes.

Fullerene C and its malonate derivatives, produced the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC).

Supraphysiological glutamine as a means of depleting intracellular amino acids to enhance pancreatic cancer chemosensitivity.

Limited efficacy of systemic therapy for pancreatic ductal adenocarcinoma (PDAC) patients contributes to high mortality. Cancer cells develop strategies to secure nutrients in nutrient-deprived conditions and chemotherapy treatment. Despite the dependency of PDAC on glutamine (Gln) for growth and survival, strategies designed to suppress Gln metabolism have limited effects.

Aptamers as Theragnostic Tools in Prostate Cancer.

Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed.

Click synthesis of novel dendronized curcumin and analogs. Strengthening of physicochemical properties toward biological applications.

Curcumin and its analogs, chalcones, and C5-monocarbonyl are molecules of great therapeutic potential, but their poor stability and hydrophobicity have hampered their extensive use in clinical trials. Therefore, significant efforts have been made in materials science to improve their physicochemical properties. In this study, we propose dendronization as a synthetic strategy to strengthen some physicochemical properties such as solubility and stability of curcumin and analogs, taking advantage of the click chemistry (CuAAC) to attach second-generation polyester dendrons to the unsaturated cores.

Hormone-Related Cancer and Autoimmune Diseases: A Complex Interplay to be Discovered.

Neoplasic transformation is a continuous process that occurs in the body. Even before clinical signs, the immune system is capable of recognizing these aberrant cells and reacting to suppress them. However, transformed cells acquire the ability to evade innate and adaptive immune defenses through the secretion of molecules that inhibit immune effector functions, resulting in tumor progression.

Dendronization: A practical strategy to improve the performance of molecular systems used in biomedical applications.

Nanomedicine is an emerging area that largely influences the efficacy of various therapies through the rational design of new materials exhibiting more targeted behavior. The synthetic effort, the amount of used material, and the cost are critical parameters to bear in mind if the production of the designed material is intended to be scaled for their widespread use. Even though materials science offers diverse options for different types of therapies, it is a difficult task to meet all the parameters mentioned above.

Inhibition of Stearoyl-CoA Desaturase by Sterculic Oil Reduces Proliferation and Induces Apoptosis in Prostate Cancer Cell Lines.

Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa.

New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil.

The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments.

Cell-Internalization SELEX of RNA Aptamers as a Starting Point for Prostate Cancer Research.

In the treatment of cancer, over the last decade different drugs delivery systems have been developed to increase therapeutic specificity to improve drug's efficacy, and safety by increasing bioavailability. Among these systems, small nucleic acid molecules with a three-dimensional structure, known as aptamers, have shown several advantages. Several approaches to design aptamers require modifications from starting libraries of DNA sequences.

Prostate Cancer Spheroids: A Three-Dimensional Model for Studying Tumor Heterogeneity.

Prostate cancer is one of the main causes of cancer and the sixth cause of death among men worldwide. One of the major challenges in prostate cancer research is cell heterogeneity defined as the different genomic and phenotypic characteristics in each individual cell making more difficult to assess the proper prostate cancer diagnosis and therapy. Tumor 3D spatial arrangement allow a strong interaction between the different cellular lineages and components which modulate cell proliferation, differentiation, and morphology.

SFRP1 increases TMPRSS2-ERG expression promoting neoplastic features in prostate cancer in vitro and in vivo.

Background: Prostate cancer (PCa) is the second cause of cancer related death in North American men. Androgens play an important role in its progression by regulating the expression of several genes including fusion ones that results from structural chromosome rearrangements. - is a fusion gene commonly observed in over 50% of PCa tumors, and its expression can be transcriptionally regulated by the androgen receptor (AR) given its androgen responsive elements.

Anthocyanins of Blue Corn and Tortilla Arrest Cell Cycle and Induce Apoptosis on Breast and Prostate Cancer Cells.

Breast and prostate cancer are frequently diagnosed neoplasias in women and men around the world. The signaling of the androgen receptor (AR) influences the development of both tumors. Since therapies focused to block the receptor's activity have not been fully effective, and have shown side effects, therapies based on natural compounds are promissory complementary alternatives in its treatment.

Antioxidant and antiproliferative activity of blue corn and tortilla from native maize.

Background: Blue corn is a cereal rich in phenolic compounds used to make blue tortillas. Tortillas are an important part of the Mexican diet. Blue corn and tortilla represent an important source of the natural antioxidants anthocyanins.

Tandem Approach to Benzothieno- and Benzofuropyridines from o-Alkynyl Aldehydes via Silver-Catalyzed 6-endo-dig Ring Closure.

An operationally simple silver-catalyzed tandem strategy for the synthesis of benzothienopyridines 7a-t and benzofuropyridines 8a-p by the reaction of o-alkynyl aldehyde 4a-t and 5a-p with tert-butylamine 6 under mild reaction conditions is described. The present methodology provides a facile conversion of easily accessible o-alkynyl aldehydes into medicinally useful heterocycles in good to excellent yields under mild and environmentally friendly reaction conditions with excellent regioselectivity. The developed chemistry has been successfully extended for the selective synthesis of C-4 deuterated benzothienopyridines 7u-v and benzofuropyridines 8q-r.