Baker, Jennifer R. published the artcileAmino Alcohol Acrylonitriles as Activators of the Aryl Hydrocarbon Receptor Pathway: An Unexpected MTT Phenotypic Screening Outcome, Quality Control of 115314-17-5, the publication is ChemMedChem (2020), 15(6), 490-505, database is CAplus and MEDLINE.
Lead (Z)-N-(4-(2-cyano-2-(3,4-dichlorophenyl)vinyl)phenyl)acetamide, 1 showed MCF-7 GI50=30 nM and 400-fold selective c.f. MCF10A (normal breast tissue). Acetamide moiety modification (13 a-g) to introduce addnl. hydrophobicity was favored with MCF-7 breast cancer cell activity enhanced at 1.3 nM. Other analogs were potent against the HT29 colon cancer cell line at 23 nM. Textbook SAR data was observed in the MCF-7 cell line, in an MTT assay, via the ortho (17 a), meta (17 b) and para (13 f). The amino alc. -OH moiety was pivotal, but no stereochem. preference noted. But, these data did not fit our homol. modeling expectations. Aberrant MTT ((3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) screening results and metabolic interference confirmed by sulforhodamine B (SRB) screening. Interfering analogs resulted in 120 and 80-fold CYP1A1 and CYP1A2 amplification, with no upregulation of SULT1A1. This is consistent with activation of the AhR pathway. Piperidine per-deuteration reduced metabolic inactivation. 3-OH / 4-OH piperidine analogs showed differential MTT and SRB activity supporting MTT assay metabolic inactivation. Data supports piperidine 3-OH, but not the 4-OH, as a CYP substrate. This family of β-amino alc. substituted 3,4-dichlorophenylacetonitriles show broad activity modulated via the AhR pathway. By SRB anal. the most potent analog was 23 b, (Z)-3-(4-(3-(4-phenylpiperidin-1-yl)-2-hydroxypropoxy)phenyl)-2-(3,4-dichlorophenyl)-acrylonitrile.
ChemMedChem published new progress about 115314-17-5. 115314-17-5 belongs to esters-buliding-blocks, auxiliary class Epoxides,Chiral,Nitro Compound,Sulfonate,Benzene, name is (R)-Oxiran-2-ylmethyl 3-nitrobenzenesulfonate, and the molecular formula is C9H9NO6S, Quality Control of 115314-17-5.
Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics