Cem YAMALİ, Halise Inci GUL, Yeliz DEMİR, Cavit KAZAZ, Ilhami GULCİN

Synthesis and bioactivities of 1-(4-hydroxyphenyl)-2-((heteroaryl)thio)ethanones as carbonic anhydrase I, II and acetylcholinesterase inhibitors

The discovery of enzyme targeting inhibitors is a popular area of drug research. Biological activities of the compounds bearing phenol and heteroaryl groups make them popular groups in drug design targeting important enzymes such as acetylcholinesterase (AChE, E.C.3.1.1.7) and carbonic anhydrases (CAs, EC 4.2.1.1). 1-(4-hydroxyphenyl)-2-((aryl)thio)ethanones as possible AChE and CAs inhibitors were synthesized, and their chemical structures were confirmed by IR, H-1 NMR, C-13 NMR, and HRMS. The compounds 2 and 4 were found potent AChE inhibitors with the Ki values of 22.13 +/- 1.96 nM and 23.71 +/- 2.95 nM, respectively, while the compounds 2 (Ki = 8.61 +/- 0.90 nM, on hCA I) and 1 (Ki = 8.76 +/- 0.84 nM, on hCA II) had considerable CAs inhibitory potency. The lead compounds may help the scientists for the rational designing of an innovative class of drug candidates targeting enzyme-based diseases.

Keywords:

Carbonic anhydrases, acetylcholinesterase, heterocyclic, phenol,

PDF

___

Akincioglu A, 2015, BIOORGAN MED CHEM, V23, P3592, DOI 10.1016/j.bmc.2015.04.019
Akincioglu A, 2013, BIOORGAN MED CHEM, V21, P1379, DOI 10.1016/j.bmc.2013.01.019
Aksu K, 2013, BIOORGAN MED CHEM, V21, P2925, DOI 10.1016/j.bmc.2013.03.077
Alterio V, 2012, CHEM REV, V112, P4421, DOI 10.1021/cr200176r
Arabaci B, 2014, MOLECULES, V19, P10103, DOI 10.3390/molecules190710103
Boztas M, 2015, J MED CHEM, V58, P640, DOI 10.1021/jm501573b
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
Bytyqi-Damoni A, 2020, J MOL STRUCT, V1202, DOI 10.1016/j.molstruc.2019.127297
Cakmak KC, 2019, TOXICOL REP, V6, P1273, DOI 10.1016/j.toxrep.2019.11.003
Cevik UA, 2019, MOLECULES, V24, DOI 10.3390/molecules24050861
Chaves S, 2020, MOLECULES, V25, DOI 10.3390/molecules25040985
El-Sayed NA, 2019, BIOORG CHEM, V93, DOI 10.1016/j.bioorg.2019.103312
ELLMAN GL, 1961, BIOCHEM PHARMACOL, V7, P88, DOI 10.1016/0006-2952(61)90145-9
Gulcin I, 2013, MINI-REV MED CHEM, V13, P408
Guney M, 2014, BIOORGAN MED CHEM, V22, P3537, DOI 10.1016/j.bmc.2014.04.007
Innocenti A, 2010, BIOORG MED CHEM LETT, V20, P5050, DOI 10.1016/j.bmcl.2010.07.038
Ivanova L, 2020, MOLECULES, V25, DOI 10.3390/molecules25081846
Kocyigit UM, 2017, BIOORG CHEM, V70, P118, DOI 10.1016/j.bioorg.2016.12.001
Li GL, 2018, EUR J MED CHEM, V148, P238, DOI 10.1016/j.ejmech.2018.01.028
Li JC, 2016, BIOORG MED CHEM LETT, V26, P3881, DOI 10.1016/j.bmcl.2016.07.017
Lineweaver H, 1934, J AM CHEM SOC, V56, P658, DOI 10.1021/ja01318a036
Mehr-un-Nisa, 2015, BIOORGAN MED CHEM, V23, P6014, DOI 10.1016/j.bmc.2015.06.051
Ozgeris B, 2016, BIOORGAN MED CHEM, V24, P2318, DOI 10.1016/j.bmc.2016.04.002
Ozgun DO, 2019, BIOORG CHEM, V84, P511, DOI 10.1016/j.bioorg.2018.12.028
Ozgun DO, 2016, J ENZYM INHIB MED CH, V31, P1498, DOI 10.3109/14756366.2016.1149479
Pradaux-Caggiano F, 2012, MEDCHEMCOMM, V3, P1117, DOI 10.1039/c2md20091k
Reddy MVR, 2010, BIOORGAN MED CHEM, V18, P2317, DOI 10.1016/j.bmc.2010.01.051
Sang ZP, 2017, BIOORG MED CHEM LETT, V27, P5046, DOI 10.1016/j.bmcl.2017.09.057
Sarikaya SBO, 2011, BIOORG MED CHEM LETT, V21, P4259, DOI 10.1016/j.bmcl.2011.05.071
Scozzafava A, 2015, J ENZYM INHIB MED CH, V30, P586, DOI 10.3109/14756366.2014.956310
Senturk M, 2009, BIOORGAN MED CHEM, V17, P3207, DOI 10.1016/j.bmc.2009.01.067
Stasiuk M, 2008, FOOD CHEM, V108, P996, DOI 10.1016/j.foodchem.2007.12.011
Sujayev A, 2020, APPL ORGANOMET CHEM, V34, DOI 10.1002/aoc.5329
Supuran CT, 2008, NAT REV DRUG DISCOV, V7, P168, DOI 10.1038/nrd2467
Supuran CT, 2016, J ENZYM INHIB MED CH, V31, P1254, DOI 10.1080/14756366.2016.1201479
Taslimi P, 2017, J ENZYM INHIB MED CH, V32, P137, DOI 10.1080/14756366.2016.1238367
Topal M, 2014, TURK J CHEM, V38, P894, DOI 10.3906/kim-1403-5
Tripathi PN, 2019, BIOORGAN MED CHEM, V27, P1327, DOI 10.1016/j.bmc.2019.02.031
VERPOORTE JA, 1967, J BIOL CHEM, V242, P4221
Yamali C, 2020, BIOORG CHEM, V96, DOI 10.1016/j.bioorg.2020.103627
Yamali C, 2018, CHEM BIOL DRUG DES, V91, P854, DOI 10.1111/cbdd.13149
Yildirim A, 2015, BIOORGAN MED CHEM, V23, P2598, DOI 10.1016/j.bmc.2014.12.054
Yin L, 2017, HETEROCYCL COMMUN, V23, P231, DOI 10.1515/hc-2016-0163