Synthesis and Human Carbonic Anhydrase I, II, IX, and XII Inhibition Studies of Sulphonamides Incorporating Mono-, Bi- and Tricyclic Imide Moieties

Abstract

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure–activity relationships (SAR) are rationalised with the help of molecular docking studies.

Phthalimide as a versatile pharmacophore scaffold: Unlocking its diverse biological activities

“…Compound 123 also showed a value of 20% against maximal electroshock (MES)-induced seizure in animals without epileptic crises (Iman et al, 2018). Davood et al therapeutic targets in various diseases, including epilepsy (Ciccone et al, 2021;Mishra et al, 2020;Thiry et al, 2007) In a recent study, Sethi et al (2021) synthesized and evaluated a series of sulfonamide-based analogs containing phthalimide moieties (126-136) (Figure 10) for their inhibitory activity against four different hCA enzymes (hCAI, hCAII, hCAIX, and hCAXII). The results showed that compounds 126-132 and 134-136 exhibited potent K i values in the range of 0.159-0.463 µM against hCAI, while phthalimides 127-132 and 134-136 showed strong inhibition against hCAII with K i values ranging from 0.0024 to 0.044 µM.…”

Design, synthesis, and biological activity of novel dithiocarbamate‐methylsulfonyl hybrids as carbonic anhydrase inhibitors

“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [ 15–24 ]…”

“…In addition, many studies brought to the literature in recent years have emphasized the strong CA inhibitory activity of this group. [15][16][17][18][19][20][21][22][23][24] Bioisosterism represents one approach used by the medicinal chemist for the rational modification of lead compounds into safer and more clinically effective agents. [25] In the context of contemporary medicinal chemistry and drug discovery, and particularly during lead optimization, isosterism and bioisosterism have been very active areas of research as their principles are directly applicable to structure optimization efforts.…”

2‐Amino thiazole derivatives as inhibitors of some metabolic enzymes: An in vitro and in silico study

“…Thus, the treatment options have genuinely focused on the amelioration of the cholinergic pathway, and for this purpose, AChE inhibitors were discovered 23 . AChE has recently become a widely used target to improve symptoms of AD 24–26 …”

“…23 AChE has recently become a widely used target to improve symptoms of AD. [24][25][26] In this study, the effects of 2-amino thiazole derivatives (Figure 1) on hCA I, hCA II isozymes, AChE and BChE enzyme activities were investigated, their selectivity rates were determined, and inhibition mechanisms were estimated by molecular docking studies.…”