{"title":"几种与NK1受体结合的低分子量3,5-双三氟甲基苯衍生物","authors":"Piotr F. J. Lipiński, Joanna Matalińska","doi":"10.32383/appdr/163051","DOIUrl":null,"url":null,"abstract":"We were interested in finding smallest possible ligands of the NK1 receptor (NK1R). Based on structural considerations and molecular docking (scoring) we selected six simple (low molecular weight, MW) 3,5-bistrifluoromethylbenzene derivatives and tested them for human NK1R affinity. The compounds turned out to have detectable but very low affinity for the receptor (IC50 > 100 μM). The discrepancy between the docking scores and the experimental affinity provoked us to perform additional tests of AutoDock Vina scoring function performance against NK1R. The scoring function did not differentiate low MW-low affinity from low MW-high affinity binders, while it underestimated affinity of low MW-high affinity in comparison to high MW-high affinity compounds. The scoring function did not achieve satisfactory performance in discerning low MW-low affinity and low MW-high affinity binders from the sets of decoys. Analysis of molecular dynamics simulation of one of the studied compounds with NK1R suggests that docking might overestimate strength of the H-bond interaction.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NK1 receptor binding of a few low molecular weight 3,5-bistrifluoromethylbenzene derivatives\",\"authors\":\"Piotr F. J. Lipiński, Joanna Matalińska\",\"doi\":\"10.32383/appdr/163051\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"We were interested in finding smallest possible ligands of the NK1 receptor (NK1R). Based on structural considerations and molecular docking (scoring) we selected six simple (low molecular weight, MW) 3,5-bistrifluoromethylbenzene derivatives and tested them for human NK1R affinity. The compounds turned out to have detectable but very low affinity for the receptor (IC50 > 100 μM). The discrepancy between the docking scores and the experimental affinity provoked us to perform additional tests of AutoDock Vina scoring function performance against NK1R. The scoring function did not differentiate low MW-low affinity from low MW-high affinity binders, while it underestimated affinity of low MW-high affinity in comparison to high MW-high affinity compounds. The scoring function did not achieve satisfactory performance in discerning low MW-low affinity and low MW-high affinity binders from the sets of decoys. Analysis of molecular dynamics simulation of one of the studied compounds with NK1R suggests that docking might overestimate strength of the H-bond interaction.\",\"PeriodicalId\":7147,\"journal\":{\"name\":\"Acta poloniae pharmaceutica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2023-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta poloniae pharmaceutica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/163051\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta poloniae pharmaceutica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.32383/appdr/163051","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
NK1 receptor binding of a few low molecular weight 3,5-bistrifluoromethylbenzene derivatives
We were interested in finding smallest possible ligands of the NK1 receptor (NK1R). Based on structural considerations and molecular docking (scoring) we selected six simple (low molecular weight, MW) 3,5-bistrifluoromethylbenzene derivatives and tested them for human NK1R affinity. The compounds turned out to have detectable but very low affinity for the receptor (IC50 > 100 μM). The discrepancy between the docking scores and the experimental affinity provoked us to perform additional tests of AutoDock Vina scoring function performance against NK1R. The scoring function did not differentiate low MW-low affinity from low MW-high affinity binders, while it underestimated affinity of low MW-high affinity in comparison to high MW-high affinity compounds. The scoring function did not achieve satisfactory performance in discerning low MW-low affinity and low MW-high affinity binders from the sets of decoys. Analysis of molecular dynamics simulation of one of the studied compounds with NK1R suggests that docking might overestimate strength of the H-bond interaction.
期刊介绍:
The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General.
A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.