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Background: Alzheimer's disease (AD) is one of the most common forms of dementia, is characterized by memory loss and cognitive impairment that affects more than 30 million people worldwide. The pathogenesis of Alzheimer's disease is primary driven by brain accumulation of the amyloid ß peptide generated from the amyloid-ß precursor protein (APP) via cleavages by ß- and -secretase. In this study, we propose an approach by molecular docking to select compounds as -secretase inhibitors for decreasing the APP generation. Methods: We selected potential -secretase inhibitors by molecular docking in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in presenilin-1 (PS-1), using a chemical library of over 500,000 compounds. Results: Eight compounds (AZ1 - AZ8) were selected by molecular docking to develop -secretase inhibitors for decreasing the APP generation. Conclusion: AZ1 - AZ8 compounds could be interacting in the potential site between Asp257, Lue268, Asp385, Ile387, Phe388, and Leu432 amino acids in PS-1. These compounds could specifically interact in the binding pocket in PS-1 to prevent/decrease the APP generation, to develop a new drug against Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Protein Tyrosine Phosphatase 1B (PTP1B) is a protein that contributes to the development of diseases that affect millions of people worldwide. In the last five years, several studies have been carried out to develop a drug that is capable of inhibiting the functions of this protein that are related to chronic degenerative diseases and obesity. In this study, we used PTP1B as a therapeutic target to perform a molecular docking to identify compounds that specifically bind to the PTP1B human protein. After molecular docking from over 500,000 compounds, we selected the six with the highest binding score and evaluated their inhibitory effect in in vitro assays. The data showed that PT2 compound was the most potent with an IC50 value of 9 μM and a noncompetitive inhibition mechanism. According to molecular docking, this compound made specific interactions in the catalytic domain of PTP1B, that could be responsible for their inhibition capability. Furthermore, cytotoxic studies in MCF‐7 cells indicated that it could be safe for humans. Therefore, PT2 compound may be a promising new drug to attend the diseases where PTP1B has functions. [ABSTRACT FROM AUTHOR]

Background: Cancer continues worldwide. It has been reported that OTUB1, a cysteine protease, plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis by its functions on deubiquitination. Drug advances continue against new therapeutic targets. In this study we used OTUB1 to develop a specific pharmacological treatment to regulate deubiquitination by OTUB1. The aim of this research is to regulate OTUB1 functions. Methods: By molecular docking in a specific potential OTUB1 interaction site between Asp88, Cys91, and His26 amino acids, using a chemical library of over 500,000 compounds, we selected potential inhibitors of the OTUB1 catalytic site. Results: Ten compounds (OT1 - OT10) were selected by molecular docking to develop a new anti-cancer drug to decrease OTUB1 functions in cancer processes. Conclusions: OT1 - OT10 compounds could be interacting in the potential site between Asp88, Cys91, and His265 amino acids in OTUB1. This site is necessary for the deubiquitinating function of OTUB1. Therefore, this study shows another way to attack cancer. [ABSTRACT FROM AUTHOR]