Novel sulphonamides incorporating triazene moieties show powerful carbonic anhydrase I and II inhibitory properties

Abstract

A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. K I values of these sulphonamides were in the range of 21 ± 4-72 ± 2 nM towards hCA I and in the range of 16 ± 6-40 ± 2 nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (K I s of 21 nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated.

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

“…1,3-Diaryltriazene-substituted sulfonamides have been found to be potent inhibitors of the cytosolic isoform of hCA II, with low nanomolar to subnanomolar inhibition constants. [2,3] The expressed carbonic anhydrase (CA) isoenzymes are zinc (II) metalloenzymes that catalyze the hydration of carbon dioxide to hydrogen carbonate and protons. [4] Although such a transformation also occurs spontaneously, CAs' primary function is to speed up the whole mechanism.…”

Synthesis and in silico studies of triazene‐substituted sulfamerazine derivatives as acetylcholinesterase and carbonic anhydrases inhibitors

“…The designed compounds 1–9 were synthesized according to our previous study. [ 27 ] Concentrated HCl (1.5 ml) was added to the solution of sulfamerazine (4‐amino‐ N ‐(4‐methyl‐2‐pyrimidinyl)benzenesulfonamide; 5 mmol) in 3 ml water. Then the mixture was cooled to 0–5°C and stirred for 5 min.…”

“…They are one of the important groups in medicinal chemistry to design new drug candidates, as they are one of the most important linkers for many compounds and they have many roles in several applications such as biomedical applications, synthesis of natural products, and combinatorial chemistry. [ 24 ] Compounds containing a triazene structure have many activities such as antibacterial, [ 25 ] AChE inhibitory, [ 26 ] CA inhibitory, [ 27,28 ] and antitumor activities. [ 29 ] In addition, the triazene moiety is an isostere of the carbamate group that is one of the most important classes of AChE inhibitors.…”

“…[ 26,40 ] Furthermore, some 1,3‐diaryltriazene core‐bearing sulfonamide compounds were reported with CAs and AChE inhibitory effects. [ 26–28 ] However, 1,3‐diaryltriazene‐substituted sulfathiazole derivative compounds were reported with high hCA I, hCA II, and AChE inhibitory activities with a low‐nanomolar inhibition constant. [ 26 ]…”

Synthesis, characterization, molecular docking, and biological activities of coumarin–1,2,3‐triazole‐acetamide hybrid derivatives

“…[ 7,8 ] The CAs I, II, III, VII, and XIII are cytosolic; the CAs IV, IX, XII, XIV, and XV are membrane‐bound isoforms, CAs VA and VB are mitochondrial forms, and CA VI is a secreted isoform. [ 9–11 ] Also, the human carbonic anhydrases (hCAs) IX and XII are overexpressed in cancer cells, as they are transmembrane‐bound, tumor‐associated enzymes, mainly in hypoxic tumors, with a low expression in normal cells. An anticancer agent, for exhibition of potent cytotoxicity without adverse effects, should selectively inhibit tumor‐associated hCAs IX and XII over cytosolic CAs like hCA I and II isoenzymes.…”