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Molecular docking study of A(3) adenosine receptor antagonists and pharmacophore-based drug design.

机译:A(3)腺苷受体拮抗剂的分子对接研究和基于药效团的药物设计。

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摘要

Adenosine is known to act as a neuromodulator by suppressing synaptic transmission in the central and peripheral nervous system. A(3) adenosine receptor (A(3)AR) antagonists were recently considered as potential drugs for the treatment of cardiac ischemia and inflammation diseases. To better understand the chemical features responsible for the recognition mechanism and the receptor-ligand interaction, we have performed the molecular simulation study combined with a virtual library screening process to develop novel A(3)AR antagonists. A series of A(3)AR selective antagonists, including triazolopurines, imidazopurines, pyrrolopurines, and quinazolines were employed to dock into the A(3)AR binding site via AUTODOCK software. The putative binding mode for each compound was proposed. Three main hydrophobic pockets, one hydrogen bonding with Asn250, and one pi-pi interaction with Phe168 for all antagonists were identified. The most favorable binding conformations served as the templates for pharmacophore modeling with Catalyst 4.11 and a virtually generated library have been screened for novel antagonist development.
机译:已知腺苷通过抑制中枢和周围神经系统中的突触传递而充当神经调节剂。 A(3)腺苷受体(A(3)AR)拮抗剂最近被认为是治疗心脏缺血和炎症疾病的潜在药物。为了更好地了解负责识别机制和受体-配体相互作用的化学特征,我们进行了分子模拟研究,并结合了虚拟文库筛选过程来开发新型A(3)AR拮抗剂。一系列的A(3)AR选择性拮抗剂,包括三唑并呋喃酮,咪唑嘌呤,吡咯并呋喃酮和喹唑啉被用于通过AUTODOCK软件对接至A(3)AR结合位点。提出了每种化合物的推定结合模式。对于所有拮抗剂,已鉴定出三个主要的疏水口袋,一个与Asn250氢键结合以及一个与Phe168的pi-pi相互作用。筛选了最有利的结合构象作为用Catalyst 4.11进行药效基团建模的模板,并筛选了虚拟生成的文库以开发新型拮抗剂。

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