Pharmacophore Based Virtual Screening for Identification of Novel CDK₂Inhibitors  

作　　者：Amar Issa Faten Sliman Jehad Harbali Amar Issa;Faten Sliman;Jehad Harbali(Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, University of Damascus, Damascus, Syria;Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, University of Tartous, Tartous, Syria)

机构地区：[1]Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, University of Damascus, Damascus, Syria [2]Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, University of Tartous, Tartous, Syria

出　　处：《International Journal of Organic Chemistry》2021年第2期72-89,共18页有机化学国际期刊（英文）

摘　　要：CDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span></span>}<span style="font-family:Verdana;"> is one of the most important members of Cyclin-dependent kinases. It is a critical modulator of various oncogenic signaling pathways, and its activity is vital for </span><span style="font-family:Verdana;">loss</span><span style="font-family:Verdana;"> of proliferative control during oncogenesis. This work has focused on developing a pharmacophore model for CDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span></span>}<span style="font-family:Verdana;"> inhibitors by using a dataset of known inhibitors as a pre-filter throughout the virtual screening and docking process. Consequently, the best pharmacophore model was made of one hydrogen bond acceptor, and two aromatic ring features with </span></span><span style="font-family:Verdana;">a </span><span style="font-family:Verdana;">high</span><span style="font-family:""><span style="font-family:Verdana;"> correlation value of 0.906. The validation findings proved out that the selected model can be used as a filter to screen new molecules like Enamine kinase hinge region directed library against CDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span><strong></strong></span>}<span style="font-family:Verdana;">. As a result, 69 hits were subjected to molecular docking studies. Eventually, three compounds</span></span><span style="font-family:Verdana;"> (</span><span style="font-family:""><span style="font-family:Verdana;">5909, 701 </span><span style="font-family:Verdana;">and</span><span style="font-family:Verdana;"> 8397</span></span><span style="font-family:Verdana;">) </span><span style="font-family:""><span style="font-family:Verdana;">scored good interaction energy values and strong molecCDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span></span>}<span style="font-family:Verdana;"> is one of the most important members of Cyclin-dependent kinases. It is a critical modulator of various oncogenic signaling pathways, and its activity is vital for </span><span style="font-family:Verdana;">loss</span><span style="font-family:Verdana;"> of proliferative control during oncogenesis. This work has focused on developing a pharmacophore model for CDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span></span>}<span style="font-family:Verdana;"> inhibitors by using a dataset of known inhibitors as a pre-filter throughout the virtual screening and docking process. Consequently, the best pharmacophore model was made of one hydrogen bond acceptor, and two aromatic ring features with </span></span><span style="font-family:Verdana;">a </span><span style="font-family:Verdana;">high</span><span style="font-family:""><span style="font-family:Verdana;"> correlation value of 0.906. The validation findings proved out that the selected model can be used as a filter to screen new molecules like Enamine kinase hinge region directed library against CDK<span style="white-space:nowrap;">_{</span></span>_{<span style="font-family:Verdana;">2<span style="white-space:nowrap;">}</span><strong></strong></span>}<span style="font-family:Verdana;">. As a result, 69 hits were subjected to molecular docking studies. Eventually, three compounds</span></span><span style="font-family:Verdana;"> (</span><span style="font-family:""><span style="font-family:Verdana;">5909, 701 </span><span style="font-family:Verdana;">and</span><span style="font-family:Verdana;"> 8397</span></span><span style="font-family:Verdana;">) </span><span style="font-family:""><span style="font-family:Verdana;">scored good interaction energy values and strong molec

关 键 词：CDK₂ CANCERS Docking INHIBITORS PHARMACOPHORE Virtual Screening 

分 类 号：O62[理学—有机化学]