Molecular docking, drug-likeness, and ADMET study of 1-benzyl-3-benzoylurea and its analogs against VEGFR-2

2nd International Conference on Natural Resources and Life Sciences

生态环境科学

Suhud, F.^1 ; Tjahjono, D.H.^2 ; Yuniarta, T.A.^1 ; Putra, G.S.^1 ; Setiawan, J.^1

Faculty of Pharmacy, University of Surabaya, Jalan Raya Kalirungkut, Surabaya

60294, Indonesia^1

School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung

40132, Indonesia^2

关键词: Anticancer candidate;    Anticancer drug;    Bioavailable;    Docking score;    In-silico;    Low toxicity;    Molecular docking;    VEGFR-2;   

Others  :  https://iopscience.iop.org/article/10.1088/1755-1315/293/1/012018/pdf
DOI  :  10.1088/1755-1315/293/1/012018

学科分类：环境科学（综合）

来源: IOP

【 摘 要 】

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 (-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.