Discovery of novel anti-proliferative compounds against A549 cells by virtual screening

Chem-Bio Informatics Journal

Mangamoori L Narasu²  Srinivas Kolli³  P Ajay Babu¹ 

[1] Bioinformatics Division, Translational Research Institute of Molecular Sciences (TRIMS);Centre for Biotechnology, Jawaharlal Nehru Technological University Hyderabad (JNTUH);Sri Venkateswara College of Pharmacy

关键词: ZINC database;    ZINCデータベース;    cross-docking;    クロスドッキング;    binding affinity;    結合能;    apoptosis;    アポトーシス;    A549;    MTT assay;    MTTアッセイ;   

DOI  :  10.1273/cbij.10.46

学科分类：生物化学/生物物理

来源: Chem-Bio Informatics Society

【 摘 要 】

References(26)CDK2 (Cyclin Dependent Kinase 2) acts as a potential therapeutic target in cancer and several efforts have been made to find more specific, potent and selective ATP competitive CDK2 inhibitors. In this paper, we report a virtual screening approach that resulted in 54,558 Lipinski compliant hits from ZINC database based on the features exhibited by four compounds from our previous study. Docking and scoring of all compounds using GOLD (Genetic Optimisation for Ligand Docking) software, to evaluate the affinity of binding towards CDK2 enzyme 2UZO resulted in dock scores between 41.71 - 82.33 kcal/mol. The resultant dataset of 392 hits were filtered based on the specificity between CDK2 and GSK-3β (Glycogen Synthase Kinase-3β) to obtain 17 compounds that are more specific towards CDK2. Further, re-scoring of 17 best docked poses followed by a consensus scoring approach tested with five different scoring functions such as GOLD score, CHEM score implemented in GOLD 3.1, eHiTS_score (electronic High Throughput Screening), MolDock score of Molegro software and X-Score retrieved top hits. Finally, the top ten compounds were examined for anti-proliferative effects against human lung adenocarcinoma epithelial cell line, A549 using MTT assay.

【 授权许可】

Unknown