Structural understanding of 5-(4-hydroxy-phenyl)-N-(2-(5-methoxy-1H-indol-3-yl)-ethyl)-3-oxopentanamide as a neuroprotectant for Alzheimer’s disease

Novel Positron Emission Tomography Radiotracers for Imaging Mitochondrial Complex I

“…Our recent structure−activity relationship (SAR) studies of ZCM-I-1 demonstrated that a 4-F analog of ZCM-I-1 (compound 2, Figure 2) exhibits comparable protective potency in the phenotypic screening assay. 45 The CESTA also supported its physical interaction with the NDUFV1 subunit of MC-I (Figure 3B). We also measured the binding affinity of this compound to the purified MC-I from the bovine heart using the microscale thermophoresis (MST) assay, 46 taking advantage of the autofluorescence of MC-I.…”

“…By analyzing the chemical structure of ZCM-I-1 , the logic consideration for radiolabeling would be the 5-OCH 3 group on the indole ring with a -O 11 CH 3 to maintain the intact structure of ZCM-I-1 and its physicochemical properties and favorable pharmacology toward MC-I. − However, synthetically, multistep radiochemistry, including -OH or -NH protection and deprotection reactions, is needed, and this challenge will hinder the future clinical applications. Our recent structure–activity relationship (SAR) studies of ZCM-I-1 demonstrated that a 4-F analog of ZCM-I-1 (compound 2 , Figure ) exhibits comparable protective potency in the phenotypic screening assay . The CESTA also supported its physical interaction with the NDUFV1 subunit of MC-I (Figure B).…”