Syntesis of thio- and seleno-acetamides bearing benzenesulfonamide as potent inhibitors of human carbonic anhydrase II and XII

Abstract

A novel series of thio-and seleno-acetamides bearing benzenesulfonamide were synthetized and tested as human carbonic anhydrase inhibitors. These compounds were tested for the inhibition of four human (h) isoforms, hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX/XII). Several derivatives showed potent inhibition activity in low nanomolar range such as 3a, 4a, 7a and 8a. Furthermore, based on the tail approach we explain the interesting and selective inhibition profile of compound such as 5a and 9a, which were more selective for hCA I, 9b which was selective for hCA II, 3f selective for hCA IX and finally, 3e and 4b selective for hCA XII, over the other three isoforms. They are interesting leads for the development of more effective and isoform-selective inhibitors.

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

“…8. General Procedure for the Synthesis of compound [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. A solution of 5a-b (0.2 g, 1.0 eq) in dry MeOH was treated with Et 3 N (1 eq) then the reaction mixture was cooled to 0 • C and benzaldehyde 6-15 (1 eq) was added.…”

“…The solvents were removed under reduced pressure and the title compounds were either obtained from filtration of the precipitates formed after addition of 5-10 mL of ice-cold water, followed by washing with Et 2 O (3 × 5 mL) (21,26,33) or extracted from ethyl acetate. In the latter the combined organic layers were washed with H 2 O (3 × 20 mL), dried over Na 2 SO 4 , filtered and concentrated in vacuum to give a residue that was crystallized from EtOH-Water (1:1) (17,22,25,34) or purified by silica gel column chromatography by eluting with 10%MeOH in DCM as the mobile phase (16, 18-20, 23-24, 27-30, 35).…”

“…In this contest the "tail approach" proved to be the most successful strategy within the field of Medicinal Chemistry on targeting specific CA isoforms. Such an approach makes use of the interactions occurring between the chemical moieties inserted in the CAIs tails and the amino acid residues located at the rim of the enzymatic cavity, which have the lowest homology sequences among the CA isoforms of the α-class [17,[21][22][23][24][25][26][27]. An important structural consideration is the role of the linker connecting the tail and the warhead sections within CAI molecules in order to make use of the tail strategy.…”

Stability of di-butyl-dichalcogenide-capped gold nanoparticles: experimental data and theoretical insights

“…Therefore, the combination of these molecules with nanoparticles can produce materials of great technological interest. 18 Organoselenium and organotellurium compounds are very versatile, with numerous opportunities for research, development and applications such as antimicrobial activity, 19 cancer treatment, 20 glaucoma treatment, 21 and catalysis. 22 S, Se and Te atoms have high affinity for noble metals such as silver, gold and platinum; also, due to their chemical similarity, both tellurium and selenium may eventually replace sulfur in a large number of molecules without increasing their toxicity or causing great environmental impact.…”

Effect of the position of a methoxy substituent on the antimicrobial activity and crystal structures of 4-methyl-1,6-diphenylpyrimidine-2(1H)-selenone derivatives

“…Selenoorganic compounds show ISSN 2053ISSN -2296 # 2020 International Union of Crystallography various biological activities, e.g. antimicrobial, antioxidant and anticancer (Domínguez-Á lvarez et al, 2016;Luo et al, 2012;Mosolygó et al, 2019;Shaaban et al, 2015;Tanini et al, 2019). It was reported previously that some pyrimidinone derivatives show antimicrobial activity (Brands et al, 2003;Edrees et al, 2010;Aly & Kamal, 2012;Cherif et al, 2015).…”