Biomaterial Database

Ureidosulfocoumarin Derivatives As Selective and Potent Carbonic Anhydrase IX and XII Inhibitors. 2022

Priti Singh, and Dilep Kumar Sigalapalli, and Nerella Sridhar Goud, and Baijayantimala Swain, and Santosh Kumar Sahoo, and Andrea Angeli, and Afzal B Shaik, and Venkata Madhavi Yaddanapudi, and Claudiu T Supuran, and Mohammed Arifuddin

Department of Chemical Sciences, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, Telangana State, India.

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.

UI	MeSH Term	Description	Entries
D007527	Isoenzymes	Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.	Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D009369	Neoplasms	New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.	Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D010075	Oxathiins		Oxathins
D002256	Carbonic Anhydrases	A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1.	Carbonate Dehydratase,Carbonic Anhydrase,Anhydrases, Carbonic,Dehydratase, Carbonate
D002257	Carbonic Anhydrase Inhibitors	A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.	Carbonate Dehydratase Inhibitor,Carbonate Dehydratase Inhibitors,Carbonic Anhydrase Inhibitor,Carboxyanhydrase Inhibitor,Carboxyanhydrase Inhibitors,Anhydrase Inhibitor, Carbonic,Dehydratase Inhibitor, Carbonate,Inhibitor, Carbonate Dehydratase,Inhibitor, Carbonic Anhydrase,Inhibitor, Carboxyanhydrase,Inhibitors, Carbonate Dehydratase,Inhibitors, Carbonic Anhydrase,Inhibitors, Carboxyanhydrase
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071231	Carbonic Anhydrase IX	A carbonic anhydrase and transmembrane protein that consists of an N-terminal PROTEOGLYCAN-like domain, a catalytic region, a single-pass transmembrane domain, and a short intracellular tail. It functions as a dimer and is expressed primarily by cells of the GASTROINTESTINAL TRACT; BILE DUCT EPITHELIUM; and GALL BLADDER. It is expressed at high levels in many solid tumors, especially CLEAR CELL RENAL CARCINOMA, in response to CELL HYPOXIA.	CAIX Protein,Carbonic Anhydrase 9
D000951	Antigens, Neoplasm	Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.	Neoplasm Antigens,Tumor Antigen,Tumor Antigens,Antigen, Tumor,Antigens, Tumor
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014508	Urea	A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.	Basodexan,Carbamide,Carmol