Abstract
The antileukemia cancer activity of organic compounds analogous to ellipticine representes a critical endpoint in the understanding of this dramatic disease. A molecular modeling simulation on a dataset of 23 compounds, all of which comply with Lipinski’s rules and have a structure analogous to ellipticine, was performed using the quantitative structure activity relationship (QSAR) technique, followed by a detailed docking study on three different proteins significantly involved in this disease (PDB IDs: SYK, PI3K and BTK). As a result, a model with only four descriptors (HOMO, softness, AC1RABAMBID, and TS1KFABMID) was found to be robust enough for prediction of the antileukemia activity of the compounds studied in this work, with an R2 of 0.899 and Q2 of 0.730. A favorable interaction between the compounds and their target proteins was found in all cases; in particular, compounds 9 and 22 showed high activity and binding free energy values of around −10 kcal/mol. Theses compounds were evaluated in detail based on their molecular structure, and some modifications are suggested herein to enhance their biological activity. In particular, compounds 22_1, 22_2, 9_1, and 9_2 are indicated as possible new, potent ellipticine derivatives to be synthesized and biologically tested.
Highlights
Cancer disease represents one of the most significant health problems in the world, being the second most common cause of death around the planet [1,2]
Data, 37% of cancer cases are reported in this region, and are associated with the limited development of technology and industry related to the treatment of this disease in these countries [3]
Molecules 2020, 25, 24 cancer is considered a rare disease, with between 0.5% and 3% of the malign neoplasms reported around the world found in children
Summary
Cancer disease represents one of the most significant health problems in the world, being the second most common cause of death around the planet [1,2]. Molecules 2020, 25, 24 cancer is considered a rare disease, with between 0.5% and 3% of the malign neoplasms reported around the world found in children. This cancer type represents a significant public health problem due to the high probability of death in children, which generates a tremendous social impact on the families [4]. In this respect, leukemia is the principal childhood cancer. In Latin America, the statistics is alarming: in Colombia, leukemia is responsible for around 49% of cancer deaths, while in Mexico, this kind of cancer is responsible for
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