Discovery of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agents: virtual screening and molecular dynamic studies.

IF 2.3 3区 环境科学与生态学 Q3 CHEMISTRY, MULTIDISCIPLINARY SAR and QSAR in Environmental Research Pub Date : 2024-11-28 DOI:10.1080/1062936X.2024.2432009
S Dhiman, S Gupta, S K Kashaw, S Chtita, S Kaya, A A Almehizia, V Asati
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Abstract

CDK/Cyclins are dysregulated in several human cancers. Recent studies showed inhibition of CDK4/6 was responsible for controlling cell cycle progression and cancer cell growth. In the present study, atom-based and field-based 3D-QSAR, virtual screening, molecular docking and molecular dynamics studies were done for the development of novel pyrrolo[2,3-d]pyrimidine (P2P) derivatives as anticancer agents. The developed models showed good Q2 and r2 values for atom-based 3D-QSAR, which were equal to 0.7327 and 0.8939, whereas for field-based 3D-QSAR the values were 0.8552 and 0.6255, respectively. Molecular docking study showed good-binding interactions with amino acid residues such as VAL-101, HIE-100, ASP-104, ILE-19, LYS-147 and GLU-99, important for CDK4/6 inhibitory activity by using PDB ID: 5L2S. Pharmacophore hypothesis (HHHRR_1) was used in the screening of ZINC database. The top scored ZINC compound ZINC91325512 showed binding interactions with amino acid residues VAL-101, ILE-19, and LYS-147. Enumeration study revealed that the screened compound R1 showed binding interactions with VAL 101 and GLN 149 residues. Furthermore, the Molecular dynamic study showed compound R1, ZINC91325512 and ZINC04000264 having RMSD values of 1.649, 1.733 and 1.610 Å, respectively. These ZINC and enumerated compounds may be used for the development of novel pyrrolo[2,3-d]pyrimidine derivatives as anticancer agent.

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发现作为抗癌剂的新型吡咯并[2,3-d]嘧啶衍生物:虚拟筛选和分子动力学研究。
CDK/Cyclins 在几种人类癌症中出现失调。最近的研究表明,CDK4/6 的抑制作用可控制细胞周期的进展和癌细胞的生长。在本研究中,为开发新型吡咯并[2,3-d]嘧啶(P2P)衍生物作为抗癌药物,进行了基于原子和基于场的三维-QSAR、虚拟筛选、分子对接和分子动力学研究。所开发的模型显示,基于原子的 3D-QSAR 的 Q2 值和 r2 值良好,分别为 0.7327 和 0.8939,而基于场的 3D-QSAR 的 Q2 值和 r2 值分别为 0.8552 和 0.6255。分子对接研究表明,通过使用 PDB ID:5L2S.在筛选 ZINC 数据库时使用了药效假说 (HHHRR_1)。得分最高的 ZINC 化合物 ZINC91325512 与 VAL-101、ILE-19 和 LYS-147 氨基酸残基有结合相互作用。枚举研究显示,筛选出的化合物 R1 与 VAL 101 和 GLN 149 残基有结合作用。此外,分子动力学研究显示,化合物 R1、ZINC91325512 和 ZINC04000264 的 RMSD 值分别为 1.649、1.733 和 1.610 Å。这些 ZINC 和列举的化合物可用于开发新型吡咯并[2,3-d]嘧啶衍生物作为抗癌剂。
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来源期刊
CiteScore
5.20
自引率
20.00%
发文量
78
审稿时长
>24 weeks
期刊介绍: SAR and QSAR in Environmental Research is an international journal welcoming papers on the fundamental and practical aspects of the structure-activity and structure-property relationships in the fields of environmental science, agrochemistry, toxicology, pharmacology and applied chemistry. A unique aspect of the journal is the focus on emerging techniques for the building of SAR and QSAR models in these widely varying fields. The scope of the journal includes, but is not limited to, the topics of topological and physicochemical descriptors, mathematical, statistical and graphical methods for data analysis, computer methods and programs, original applications and comparative studies. In addition to primary scientific papers, the journal contains reviews of books and software and news of conferences. Special issues on topics of current and widespread interest to the SAR and QSAR community will be published from time to time.
期刊最新文献
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