Abstract
Leukemias are neoplasms that affect hematopoietic cells, which are developed by genetic alterations (mutations) that lead to the loss of proliferation control mechanisms (maturation and/or cell death). The α4β1 integrin receptor is a therapeutic target for inflammation, autoimmune diseases and lymphoid tumors. This study was carried out to search through the antagonists-based virtual screening for α4β1 receptor. Initially, seventeen (17) structures were selected (based on the inhibitory activity values, IC50) and the structure with the best value was chosen as the pivot. The pharmacophoric pattern was determined from the online PharmaGist server and resulted in a model of score value equal to 97.940 with 15 pharmacophoric characteristics that were statistically evaluated via Pearson correlations, principal component analysis (PCA) and hierarchical clustering analysis (HCA). A refined model generated four pharmacophoric hypotheses totaling 1.478 structures set of Zinc_database. After, the pharmacokinetic, toxicological and biological activity predictions were realized comparing with pivot structure that resulted in five (ZINC72088291, ZINC68842860, ZINC14365931, ZINC09588345 and ZINC91247798) structures with optimal in silico predictions. Therefore, future studies are needed to confirm antitumor potential activity of molecules selected this work with in vitro and in vivo assays.
Highlights
It is estimated that cancer alone corresponds to 21% of the total amount of deaths registered.For the 30 years, the World Health Organization (WHO) has estimated 75 million people will be living with cancer
Leukemias are neoplasms that affect stem cells which are developed by genetic alterations through proliferation control mechanisms, and can be divided into four main groups: acute myeloid (AML), chronic myeloid (CML), acute lymphoid (ALL) and chronic lymphoid (CLL), being differentiated by some properties such as: cellular origin, evolution and response to therapy [2,3]
T cells are a type of lymphocyte that grow in the thymus and are responsible for the immunological recognition of pathogens
Summary
It is estimated that cancer alone corresponds to 21% of the total amount of deaths registered. For the 30 years, the World Health Organization (WHO) has estimated 75 million people will be living with cancer. Leukemias are neoplasms that affect stem cells which are developed by genetic alterations through proliferation control mechanisms (maturation and/or cell death), and can be divided into four main groups: acute myeloid (AML), chronic myeloid (CML), acute lymphoid (ALL) and chronic lymphoid (CLL), being differentiated by some properties such as: cellular origin, evolution and response to therapy [2,3]. Acute lymphoid leukemia results in the excessive production of blasts and lymphoid-type cells of. T cells are a type of lymphocyte that grow in the thymus and are responsible for the immunological recognition of pathogens. The extracellular proteins, captured by antigen-presenting cells (APCs), are degraded and resulting peptides bind to T-cell receptors (TCRs) determining the immune response [6,7]
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