Editorial on the Research Topic
Metalloenzymes: Potential Drug TargetsMetalloenzymes have an important role in the regulation of many biological functions. Overexpressed and/or reduced secretion of such enzymes lead to different complications of clinical interest. The metal ions present in enzymes control the structure, folding, and functions of such proteins. The protein data bank (PDB) revealed that over 50% of proteins contain metal ions (Solomon et al., 1996). The development of metalloenzyme inhibitors are of interest in the treatment of various diseases. The interaction of ligands, i.e., compounds as inhibitors with target proteins via active sites provide a means of curing diseases. Most aptly, the inhibitors reported by academic or pharmaceutical usage of small molecules as inhibitors provide a rapid and viable way to treat diseases. Urease is a ubiquitous metalloenzyme, produced by various cell types from plants, fungi, and bacteria, etc., that bears a nickel atom in its active pocket. It hydrolyzes the urea into ammonia and carbamate which further decompose to ammonia and CO 2 . The overexpression of urease was known to be linked with ulcers, hepatic coma, and formation of urinary stones (Upadhyay, 2012;Kappaun et al., 2018).Carbonic anhydrase with zinc metal ion catalyze the hydration of CO 2 with water to produce hydrogen carbonate and H + ions (Alvarez-Leefmans and Delpire, 2009). The hydration reaction involves the nucleophilic attack of the metal-bounded hydroxy (OH) group with the carbon (C) atom of carbon dioxide species (Silverman and Lindskog, 1988). The coordination of carbonic anhydrases (CAs) with metal ion occurs at active sites via binding with histidine, cysteine, and/or glutamine residues to form a tetrahedral shape (Steiner et al., 1975). The inhibitors of CAs have been employed as diuretic and antiglaucoma agents as well as anti-obesity and anticancer agents (Supuran, 2008).Furthermore, ubiquitous ecto-nucleotidases such as 1) nucleoside triphosphate diphosphohydrolases (NTPDases), 2) nucleotide pyrophosphatase/phosphodiesterases (NPPs), 3) alkaline phosphatases (APs or ALPs), and 4) ecto-5′-nucleotidase (e5′NT) are all responsible for the integrity of proper cell functioning (Supuran, 2008). The NPPs possess zinc (Zn 2+ ) metal ion at active sites while the e5′NT has additionally magnesium ion (Mg 2+ ) at the active site. The overexpression of surface-located ecto-enzymes hydrolyzing nucleotides causes various complications which affect different functions such as cell proliferation, apoptosis as well as degenerative, neurological, and immunological responses. In the current issue, Baqi et al. reported the use of anthraquinone derivatives as NTPDase inhibitors which showed selectivity towards NTPDase2 and -3. The compound, 1-amino-4-(9-phenanthrylamino)-9,10-dioxo-9,10-dihydroanthracene-2-sulfonate, with an IC 50 value of 539 nM was found to be a potent inhibitor of NTPDase2, while the anthraquinone, 1-amino-4-[3-(4,6-dichlorotriazin-2-ylamino)-4-sulfophenylamino]-9,10-dioxo-