Abstract
In silico study was performed to predict the possibility of 1-benzyl-3-benzoylurea and 22 analogs as anticancer drug candidates, via VEGFR2 inhibition. Molecular docking studies against VEGFR2 receptor revealed that all of designed compounds have better score than the lead compound, of which three analogs (p-nitro, p-methoxy, and p-ethyl) were considered optimal among other compounds (< -90 kcal mol−1). However, this result was not comparable to lenvatinib, which acts as native ligand of the receptor (-118.62 kcal mol−1). Docking poses analysis showed that 1-benzyl-3-benzoylurea analogs failed to completely occupy VEGFR2 binding site. Therefore, it is argued that this has caused the non-optimal docking score of designed compounds. Furthermore, these compounds passed five different drug-likeness criteria successfully and were predicted to be orally bioavailable in rat. Ultimately, most of the analogs were predicted to have good ADMET characteristics, notably in terms of GI absorption and the absence of P-gp interaction, and low toxicity in rat. This study can be used as a starting point to validate this model by synthesis, in vitro and in vivo assay to validate the activity of 1-benzyl-3-benzoylurea and its analogs as potential anticancer candidate.
Highlights
Cancer is a terminology which is commonly used to describe the abnormality in cell growth and division [1]
Docking poses analysis showed that 1-benzyl-3-benzoylurea analogs failed to completely occupy VEGFR2 binding site
This study can be used as a starting point to validate this model by synthesis, in vitro and in vivo assay to validate the activity of 1-benzyl-3-benzoylurea and its analogs as potential anticancer candidate
Summary
Cancer is a terminology which is commonly used to describe the abnormality in cell growth and division [1]. In 2012, the number of population with cancer has reached 14.1 × 106 people, with 8.2 × 106 mortality [2]. In Indonesia itself, the prevalence of cancer is 1.4 % of total population [3]. Hydroxyurea has been used for decades and still possesses valuable therapeutic activity against several type of cancer. This hydrophilic compund is distributed evenly in the human body fluid. Under physiologic condition (pH 7.4), the majority ofhydroxyurea will undergo ionization, reducing its ability to penetrate biological membrane. This condition will significantly diminished its biological activity [4]
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