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Molecular docking, drug-likeness, and ADMET study of 1-benzyl-3-benzoylurea and its analogs against VEGFR-2
Suhud F.a, Tjahjono D.H.b, Yuniarta T.A.a, Putra G.S.a, Setiawan J.a
a Faculty of Pharmacy, University of Surabaya, Surabaya, 60294, Indonesia
b School of Pharmacy, Bandung Institute of Technology, Bandung, 40132, Indonesia
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]© 2019 Published under licence by IOP Publishing Ltd.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.[/vc_column_text][vc_empty_space][vc_separator css=".vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}"][vc_empty_space][megatron_heading title="Author keywords" size="size-sm" text_align="text-left"][vc_column_text]Anticancer candidate,Anticancer drug,Bioavailable,Docking score,In-silico,Low toxicity,Molecular docking,VEGFR-2[/vc_column_text][vc_empty_space][vc_separator css=".vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}"][vc_empty_space][megatron_heading title="Indexed keywords" size="size-sm" text_align="text-left"][vc_column_text]Anticancer candidate,arylurea derivatives,in silico study,VEGFR-2 inhibitor[/vc_column_text][vc_empty_space][vc_separator css=".vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}"][vc_empty_space][megatron_heading title="Funding details" size="size-sm" text_align="text-left"][vc_column_text]This research was supported by Ministry of Research, Technology, and Higher Eduation of the Republic of Indonesia (Grant No: 120/SP2H/LT/DRPM/2018). The authors would also like to show the author gratitude to Prof. Siswandono (Universitas Airlangga) for the possibility to use Molegro in this research.[/vc_column_text][vc_empty_space][vc_separator css=".vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}"][vc_empty_space][megatron_heading title="DOI" size="size-sm" text_align="text-left"][vc_column_text]https://doi.org/10.1088/1755-1315/293/1/012018[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]