1571901-95-5Relevant academic research and scientific papers
6-substituted sulfocoumarins are selective carbonic anhdydrase IX and XII Inhibitors with significant cytotoxicity against colorectal cancer cells
Grandane, Aiga,Tanc, Muhammet,Di Cesare Mannelli, Lorenzo,Carta, Fabrizio,Ghelardini, Carla,?alubovskis, Raivis,Supuran, Claudiu T.
, p. 3975 - 3983 (2015)
6-Substituted sulfocoumarins bearing the carboxamido, trimethylammonium as well as the cyano and methoxy moieties with interesting inhibitory activity/selectivity against the tumor associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII are
Synthesis of 6-aryl-substituted sulfocoumarins and investigation of their carbonic anhydrase inhibitory action
Grandane, Aiga,Tanc, Muhammet,?alubovskis, Raivis,Supuran, Claudiu T.
, p. 1430 - 1436 (2015)
A series of 6-aryl-substituted 1,2-benzoxathiine 2,2-dioxides was obtained by reacting 6-iodo-sulfocoumarin with arylboronic acids in Suzuki cross-coupling conditions. The new sulfocoumarins incorporating various substituted phenyl moieties in position 6 of the heterocyclic ring were investigated for the inhibition of four human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms with medicinal chemistry applications, the cytosolic hCA I and II, and the transmembrane, tumor-associated hCA IX and XII. The aryl-substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms hCA I and II (KIs >10 μM) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 9.0 to 95.3 nM against hCA IX, and between 3.5 and 14.2 nM against hCA XII. As hCA IX and XII are validated anti-tumor targets, such sulfocoumarin, isoform-selective inhibitors may be useful for identifying suitable drug candidates for further clinical trials of this class of pharmacologic agents.
Synthesis of 6-tetrazolyl-substituted sulfocoumarins acting as highly potent and selective inhibitors of the tumor-associated carbonic anhydrase isoforms IX and XII
Grandane, Aiga,Tanc, Muhammet,Zalubovskis, Raivis,Supuran, Claudiu T.
, p. 1522 - 1528 (2014/03/21)
A series of 6-substituted sulfocoumarins incorporating substituted-1,2,3,4- tetrazol-5-yl moieties were synthesized by reaction of 6-iodo-sulfocoumarin and the corresponding tetrazole via the CH activation reaction. The new sulfocoumarins incorporating alkyl and substituted aryl moieties at the 1-position of the tetrazole, were investigated for the inhibition of four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, the cytosolic hCA I and II; and the transmembrane, tumor-associated hCA IX and XII. The tetrazole- substituted sulfocoumarins did not inhibit the ubiquitous, off-target cytosolic isoforms (KIs >10 μM) but showed effective inhibition against the two transmembrane CAs, with KIs ranging from 6.5 to 68.6 nM against hCA IX, and between 4.3 and 59.8 nM against hCA XII. As hCA IX and XII are validated anti-tumor targets, such prodrug, isoform-selective inhibitors as the sulfocoumarins reported here, may be useful for identifying suitable drug candidates for clinical trials.
