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Synthesis, characterization, and SAR of arylated indenoquinoline‐based cholinesterase and carbonic anhydrase inhibitors
Author(s) -
Ekiz Makbule,
Tutar Ahmet,
Ökten Salih,
Bütün Burcu,
Koçyiğit Ümit M.,
Taslimi Parham,
Topçu Gülaçtı
Publication year - 2018
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201800167
Subject(s) - butyrylcholinesterase , tacrine , acetylcholinesterase , chemistry , carbonic anhydrase , cholinesterase , enzyme , carbonic anhydrase i , aché , stereochemistry , carbonic anhydrase ii , biochemistry , pharmacology , medicine
We report the synthesis of bromoindenoquinolines ( 15a – f ) by Friedlander reactions in low yields (13–50%) and the conversion of the corresponding phenyl‐substituted indenoquinoline derivatives 16 – 21 in high yields (80–96%) by Suzuki coupling reactions. To explore the structure–activity relationship (SAR), their inhibition potentials to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and human carbonic anhydrase cyctosolic (hCA I and II) enzymes were determined. Monophenyl ( 16 – 18 ) indenoquinolines significantly inhibited the AChE and BChE enzymes in ranges of IC 50 37–57 nM and 84–93 nM, respectively, compared with their starting materials 15a–c and reference compounds (galanthamine and tacrine). On the other hand, these novel arylated indenoquinoline‐based derivatives were effective inhibitors of the BChE, hCA I and II, BChE and AChE enzymes with K i values in the range of 37 ± 2.04 to 88640 ± 1990 nM for AChE, 120.94 ± 37.06 to 1150.95 ± 304.48 nM for hCA I, 267.58 ± 98.05 to 1568.16 ± 438.67 nM for hCA II, and 84 ± 3.86 to 144120 ± 2910 nM for BChE. As a result, monophenyl indenoquinolines 16 – 18 may have promising anti‐Alzheimer drug potential and 3,8‐dibromoindenoquinoline amine ( 15f ) can be novel hCA I and hCA II enzyme inhibitors.