67326-25-4Relevant articles and documents
Ureidosulfocoumarin Derivatives As Selective and Potent Carbonic Anhydrase IX and XII Inhibitors
Angeli, Andrea,Arifuddin, Mohammed,Kumar Sahoo, Santosh,Kumar Sigalapalli, Dilep,Madhavi Yaddanapudi, Venkata,Shaik, Afzal B.,Singh, Priti,Sridhar Goud, Nerella,Supuran, Claudiu T.,Swain, Baijayantimala
, (2021/12/27)
Owing to severe allergic reactions (anaphylaxis) and resistance exhibited by sulfonamide-based carbonic anhydrase (CA) inhibitors, non-classical or non-sulfonamide CA inhibitors are gaining increased attention by medicinal chemists. In this context, we report the design and synthesis of 30 new non-sulfonamide sulfocoumarin derivatives as CA inhibitors. They were investigated against hCA I and II (cytosolic isozymes) as well as hCA IX and XII (transmembrane, tumor-associated enzymes). All compounds showed prominent selectivity for the tumor-associated isoenzymes hCA IX and XII over the cytosolic isoenzymes hCA I and II. Among all synthesized compounds, 1-(2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)-3-(o-tolyl)urea(5 j)and1-(3-fluorophenyl)-3-(8-methoxy-2,2-dioxidobenzo[e][1,2]oxathiin-6-yl)urea(5 q)were found to be more potent and to have better inhibition constant values against hCA IX than the standard acetazolamide (AAZ), with Ki values of 23.6 and 23.3 nM, respectively. All other compounds were found to be active under Ki=920 nM against hCA IX and XII.This study provides a new perspective for the future development of non-sulfonamide derivatives as selective CA inhibitors.
Sulfocoumarin-, Coumarin-, 4-Sulfamoylphenyl-Bearing Indazole-3-carboxamide Hybrids: Synthesis and Selective Inhibition of Tumor-Associated Carbonic Anhydrase Isozymes IX and XII
Angapelly, Srinivas,Sri Ramya,Angeli, Andrea,Supuran, Claudiu T.,Arifuddin, Mohammed
, p. 1578 - 1584 (2017/10/16)
A series of sulfocoumarin-, coumarin-, and 4-sulfamoylphenyl-bearing indazole-3-carboxamide hybrids were synthesized and investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Compounds 6 a–g (amide derivatives) and 7 a–h (triazoles) act as “prodrugs”, and their hydrolysis products are the de facto CA inhibitors. These compounds displayed sub-micromolar to high-nanomolar inhibitory activity against hCA isoforms IX and XII, which were recently validated as antitumor drug targets. Moreover, no inhibition of the off-target hCA I and II isoforms was observed. Compounds 8 a–f (another set of triazoles) exhibited nanomolar inhibition against hCA isoforms I, II, IX and XII, among which compounds 8 c, 8 d, and 8 f were found to inhibit the tumor-associated hypoxia-induced hCA isoform IX with Ki values of 1.8, 2.3, and 2.0 nm respectively. Further exploration of these compounds could be useful for the development of novel antitumor agents with selective mechanisms of CA inhibitory action.
Glyoxalase 1 and 2 enzyme inhibitory activity of 6-sulfamoylsaccharin and sulfocoumarin derivates
Makrecka, Marina,Zalubovskis, Raivis,Vavers, Edijs,Ivanova, Jekaterina,Grandane, Aiga,Dambrova, Maija
, p. 410 - 414 (2013/07/26)
The glyoxalase enzymes represent a cellular defence system against the accumulation of cytotoxic α-oxoaldehydes leading to apoptosis. The potential of glyoxalase inhibitors to act as novel anti-cancer agents for drugresistant tumours that over-express gly
