Synthesis and biological activity of novel thiourea derivatives as carbonic anhydrase inhibitors

Abstract

A new series of chiral thiourea derivatives (5a-5c) and thiourea containing benzimidazole moieties (9b-9e) were synthesized from different amino acids (l-valine, l-isoleucine, l-methionine, l-phenylalanine, and d-phenylglycine). The compounds were characterized and tested against the two most studied members of the pH regulatory enzyme family, carbonic anhydrase (CA, EC 4.2.1.1). KI values of the novel compounds were measured in the range of 3.4-73.6 μM for hCA I isozyme and 8.7-1.44.2 μM for hCA II isozyme, respectively. Phenol was also tested as standard in order to understand the structure activity relationship and the clinically used sulfonamide acetazolamide was tested for comparison reasons. All of the compounds exhibited competitive inhibition with 4-nitrophenylacetate as substrate.

Kinetic and docking studies of cytosolic/tumor-associated carbonic anhydrase isozymes I, II and IX with some hydroxylic compounds

“…It is interesting to note that the compounds NK-154 and NK-168 were much better hCA I inhibitors as compared to the corresponding compounds 6-10 from which they were prepared. Kinetic investigations (Lineweaver-Burk plots, data not shown) indicate that similarly to sulfonamides and inorganic anions [33][34][35][36][37][38][39] , all the investigated natural compounds act as competitive inhibitors with CO 2 as substrate (i.e. they bind in different regions of the active site cavity as compared to the substrate).…”

Crystal structure of 3-(4-chlorophenyl)-1,1-dimethylthiourea, C9H11ClN2S

“…Some derivatives show interesting applications as biologically active compounds [12][13][14][15][16][17].…”

1,1′-(Ethane-1,2-diyl)bis[3-(4-chlorobenzoyl)thiourea]

“…Multipodal thiourea compounds are expected to be useful for molecular recognition studies and as ionophores for sensor development due to the nucleophilic nature of the sulfur atoms. In addition, the biological properties of thiourea are well known (Korkmaz et al, 2015). 1,1 0 -(Ethane-1,2-diyl)bis(3-phenylthiourea) is one of the few reported bisthiourea structures with an ethylene group as linker (Pansuriya et al, 2011).…”