2-(Phenylsulfonyl)quinoline N -hydroxyacrylamides as potent anticancer agents inhibiting histone deacetylase

Effect of 3-subsitution of quinolinehydroxamic acids on selectivity of histone deacetylase isoforms

“…b Selectivity ratio: selectivity ratio of HDAC subtypes over HDAC6. [27] 0.78 ± 0.07 0.13 ± 0.01 Ã IC 50 values higher than 10 lM are estimated based on the best curve fitting available.…”

“…Scheme 1 describes the synthesis of designed compounds (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), which begins with halogenation of 8-nitroquinoline (30) with N-halosuccinimide to furnish 3-halogenated 8-nitroquinolines (31a-31c). The iodine in compound 31c was replaced by a methoxy group in the presence of CuI and 1,10-phenanthroline to generate compound 31d.…”

“…All synthetic compounds (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) were tested for their anti-proliferative activity in A549 and HCT116 cells, with SAHA (N 1 -hydroxy-N 8 - phenyloctanediamide) or PXD101 ((E)-N-hydroxy-3-(3-(N-phenylsulfamoyl)phenyl)acrylamide) as reference compounds (Table 1) 27 . Cell line inhibitory results show that halogen-substituted or most aryl/heteroaryl-substituted compounds have similar cellular activity.…”

“…Compound 25, with a 3-pyridyl group at C3 of quinoline shows remarkable HDAC6 selectivity over HDAC1, 2, and 8 with selectivity ratios of 552, 276, and 379 respectively (values under IC 50 in Table 2, presented parenthetically). On the other hand, five-membered heterocycles such as furan (27,28) and thiophene (29), which act as bioisosteres of a phenyl ring, result in decrease of HDAC6 selectivity over that of HDAC 1, 2 and 8.…”

“…Our group has focussed on the development of HDAC inhibitors with various core scaffolds including indole [21][22][23][24] , indoline 25,26 , and quinoline 27,28 . In a study related of quinoline-derived compounds, we found that 2-(phenylsulfonyl)quinoline-N-hydroxyacrylamides (6) exhibit potent pan-HDAC inhibitory and antiproliferative activity 27 .…”