药效团
数量结构-活动关系
胸苷酸合酶
化学
计算生物学
广告
对接(动物)
化学空间
立体化学
药物发现
生物化学
生物
癌症
遗传学
医学
氟尿嘧啶
护理部
体外
作者
Sonu Benny,Prayaga Rajappan Krishnendu,Sunil Kumar,Vaishnav Bhaskar,Deepthi S. Manisha,Mohamed A. Abdelgawad,Mohammed M. Ghoneim,Ibrahim A. Naguib,Leena K. Pappachen,Subin Mary Zachariah,Bijo Mathew,Aneesh TP
标识
DOI:10.1080/07391102.2023.2270752
摘要
Thymidylate synthase (TS) is a crucial target of cancer drug discovery and is mainly involved in the De novo synthesis of the DNA precursor thymine. In the present study, to generate reliable models and identify a few promising molecules, we combined QSAR modelling with the pharmacophore hypothesis-generating technique. Input molecules were clustered on their similarity, and a cluster of 74 molecules with a pyrimidine moiety was chosen as the set for 3D-QSAR and pharmacophore modelling. Atom-based and field-based 3D-QSAR models were generated and statistically validated with R2 > 0.90 and Q2 > 0.75. The common pharmacophore hypothesis(CPH) generation identified the best six-point model ADHRRR. Using these best models, a library of FDA-approved drugs was screened for activity and filtered via molecular docking, ADME profiling, and molecular dynamics simulations. The top ten promising TS-inhibiting candidates were identified, and their chemical features profitable for TS inhibitors were explored.Communicated by Ramaswamy H. Sarma.
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