Synthesis, Cytotoxicity and Antiproliferative Effect of New Pyrrole Hydrazones.

Novel pyrrole-based carbohydrazide () and hydrazones (-) were synthesized, characterized, and subjected to spectroscopic studies. The hydrazones were obtained by reacting a pyrrole hydrazide with substituted pyrrole aldehydes. The initial carbohydrazide was prepared by selective hydrazinolysis of the obtained -pyrrolylcarboxylic acid ethyl ester.

Unveiling the HSF1 Interaction Network: Key Regulators of Its Function in Cancer.

Heat shock factor 1 (HSF1) plays a central role in orchestrating the heat shock response (HSR), leading to the activation of multiple heat shock proteins (HSPs) genes and approximately thousands of other genes involved in various cellular functions. In cancer cells, HSPs play a particular role in coping with the accumulation of damaged proteins resulting from dysregulated translation and post-translational processes. This proteotoxic stress is a hallmark of cancer cells and causes constitutive activation of HSR.

Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation.

Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types.

Synthesis, Hydrolytic Stability and In Vivo Biological Study of Bioconjugates of the Tetrapeptides FELL Containing Pyrrole Moiety.

Background: Bioconjugates are promising alternatives for the multiple targeting of any disease. Pyrrole heterocycle is well known with many activities and is a building block of a lot of medical drugs. On the other hand, peptides are short molecules with many advantages such as small size, ability to penetrate the cell membrane and bond-specific receptors, vectorizing potential, etc.

Combined Cytotoxic Effect of Inhibitors of Proteostasis on Human Colon Cancer Cells.

Despite significant progress in the diagnosis and treatment of colorectal cancer, drug resistance continues to be a major limitation of therapy. In this regard, studies aimed at creating combination therapy are gaining popularity. One of the most promising adjuvants are inhibitors of the proteostasis system, chaperone machinery, and autophagy.