0000000000129991
AUTHOR
Agnese Balode
Ogļskābes anhidrāžu inhibitoru sintēze
Ogļskābes anhidrāžu inhibitoru sintēze. Balode A., zinātniskie vadītāji Dr. chem. Žalubovskis R. un Dr. chem. Kļimenkovs I. Maģistra darbs, 79 lapas, 42 attēli, 25 tabulas, 49 literatūras avoti, 1 pielikums. Latviešu valodā. Darbā tika izstrādāta tioēteru sintēzes metode no benzilspirtiem vai benzilbromīdiem, tiourīnvielas un heteroarilbromīdiem. Izmantojot šo metodi tika sintezēti 2 acetiltiofēna tioēteru atvasinājumi, tiofēn-2-sulfonamīda tioēteru atvasinājumi. Veikta tiofēn 2 sulfonamīda tioēteru oksidēšana par sulfoniem. Tika sintezēti simetriski 1,3-aril bis 1,4-diaizvietoti 1,2,3-triazolilatvasinājumi. Literatūras apskatā apkopota informācija par izotiouronija sāļu sintēzes metodēm, C…
5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations.
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocycli…
Efficient Expression and Crystallization System of Cancer-Associated Carbonic Anhydrase Isoform IX.
Human carbonic anhydrase IX (CA IX) is overexpressed in a number of solid tumors and is considered to be a marker for cellular hypoxia that it is not produced in most normal tissues. CA IX contributes to the acidification of the extracellular matrix, which, in turn, favors tumor growth and metastasis. Therefore, CA IX is considered to be a promising anti-cancer drug target. However, the ability to specifically target CA IX is challenging due to the fact that the human genome encodes 15 different carbonic anhydrase isoforms that have a high degree of homology. Furthermore, structure-based drug design of CA IX inhibitors so far has been largely unsuccessful due to technical difficulties regar…