Abstract
P2 receptors are a family of transmembrane receptors activated by nucleotides and nucleosides. Two classes have been described in mammals, P2X and P2Y, which are implicated in various diseases. Currently, only P2Y12 has medicines approved for clinical use as antiplatelet agents and natural products have emerged as a source of new drugs with action on P2 receptors due to the diversity of chemical structures. In drug discovery, in silico virtual screening (VS) techniques have become popular because they have numerous advantages, which include the evaluation of thousands of molecules against a target, usually proteins, faster and cheaper than classical high throughput screening (HTS). The number of studies using VS techniques has been growing in recent years and has led to the discovery of new molecules of natural origin with action on different P2X and P2Y receptors. Using different algorithms it is possible to obtain information on absorption, distribution, metabolism, toxicity, as well as predictions on biological activity and the lead-likeness of the selected hits. Selected biomolecules may then be tested by molecular dynamics and, if necessary, rationally designed or modified to improve their interaction for the target. The algorithms of these in silico tools are being improved to permit the precision development of new drugs and, in the future, this process will take the front of drug development against some central nervous system (CNS) disorders. Therefore, this review discusses the methodologies of in silico tools concerning P2 receptors, as well as future perspectives and discoveries, such as the employment of artificial intelligence in drug discovery.
Highlights
Plants have been used as medicine for over 60,000 years and form the basis of traditional medicines worldwide, including Chinese Medicine, Korean Medicine, Kampo (Japan), Ayurveda and Unani (India) (Yuan et al, 2016)
The zebrafish P2X4 (zfP2X4) structure was compared to a dolphin and some papers mention the left flipper, right flipper, tail, body, and head when indicating the studied portion of the protein (Kawate et al, 2009; Kawate et al, 2011). These findings enabled research into new drugs to treat P2X-related diseases such as chronic inflammation and pain (Cockayne et al, 2005; Honore et al, 2006; Donnelly-Roberts and Jarvis, 2007)
The analyses revealed that they interact with the binding site of this receptor and can inhibit in vitro platelet aggregation (Maione et al, 2015)
Summary
Plants have been used as medicine for over 60,000 years and form the basis of traditional medicines worldwide, including Chinese Medicine, Korean Medicine, Kampo (Japan), Ayurveda and Unani (India) (Yuan et al, 2016). In order to understand the interactions between P2X receptors and drug-like compounds, Dal Ben et al (2015) studied the interactions of this complex using comparative model structures of human and rat P2X receptors based on a zfP2X4 crystallography structure template. Rafehi et al (2017a) developed a P2Y4 structure based on the P2Y1 receptor and selected some anthraquinone derivatives compounds to perform molecular docking.
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