Carbonic anhydrase inhibitors. Inhibition of Plasmodium falciparum carbonic anhydrase with aromatic sulfonamides: towards antimalarials with a novel mechanism of action?

Inhibition of Carbonic Anhydrase II by Thioxolone: A Mechanistic and Structural Study

“…Other uses being explored include treatment of osteoporosis and as a diagnostic tool in magnetic resonance imaging (MRI) and photon emission tomography (PET) (25). Furthermore, other R-class CA isozymes that may be therapeutically targeted by CA inhibitors are found in the prokaryotic mammalian pathogens Neisseria gonorrheae, (28)(29)(30) Helicobacter pylori (31)(32)(33), and the eukaryotic malarial parasite Plasmodium falciparum (34)(35)(36). Known R-CA inhibitors include various anions, imidazole, phenol, hydroxyurea, carboxylates, organic phosphates and phosphonates, and various sulfonamide compounds (R-C-SO 2 NH 2 ) (4,11,25).…”

Synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties

“…In the mass spectrum of 5h the molecular ion peak was observed at m/z 319 (M þ , 2). In the 1 H NMR spectrum of 5h, measured in acetone-d6, the following important signals were observed: d ¼ 3 of acetone). Spectral, optical and crystal structure data confirmed the presence of only one enantiomer in the case of chiral compounds.…”

“…However each is much more effective when given in combination with pyrimethamine or trimethoprim [2]. Apart from their previous and more recently published antimalarial activity reports [3], sulfonamides have extensively been documented for their wide variety of pharmacological activities such as antimicrobial, insulin-releasing antidiabetic, carbonic anhydrase inhibitory, anti-HIV, high ceiling diuretic, antithyroid and antitumor [4 -5]. Sildenafil citrate, another sulfonamide derivative, was approved as the first drug for treating male erectile dysfunction (ED) [6] and a second generation antimitotic sulfonamide, ER-34410, evolved again from a scaffold of antibacterial-like sulfonamides, being 2-to 3-fold more potent than E7010 in a panel of various human tumor cell lines in vitro, and unlike E7010, can be administered intravenously [7,8].…”

Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

“…In our previous studies [24,25,71] , we investigated the first library of aromatic sulfonamides, most of which were Schiff's bases derived from sulfanilamide/homosulfanilamide/4-aminoethylbenzene-sulfonamide and substituted-aromatic aldehydes, or ureido-substituted sulfonamides, some of which proved to be effective inhibitors of the parasitic enzyme pfCA. In this review, we discuss our extending the previous works for detecting potent sulfonamide CA inhibitors (CAIs) targeting malaria CAs.…”