Discovery of a novel series of indolylchalcone-benzenesulfonamide hybrids acting as selective carbonic anhydrase II inhibitors

Singh, Priti; Yadav, Parvatha Purnachander; Swain, Baijayantimala; Thacker, Pavitra S.; Angeli, Andrea; Arifuddin, Mohammed

doi:10.1016/j.bioorg.2021.104647

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…Here, acetazolamide (AAZ) was used as the standard drug. The results of F I G U R E 1 Depiction of compounds containing indole and urea derivatives as carbonic anhydrase inhibitors [8][9][10][11][12][13][14][15][16] F I G U R E 2 Illustration of the design of the target molecules using the tail approach the inhibiton assay of the synthesized compounds against different hCA isoforms are summarized in Table 1.…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

“…Various reports have shown that indole has good CAI activity, with excellent K i values (Figure 1). [8][9][10][11][12][13][14][15][16] Furthermore, the ureido moieties incorporated with benzenesulfonamides are reported as interesting classes of CA inhibitors (CAIs). Moreover, the presence of a urea functionality in the zinc-binding group represents the most recent and promising trend in the design of CAIs (Figure 1).…”

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confidence: 99%

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Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors

Singh

Choli

Swain

et al. 2021

Archiv der Pharmazie

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Indole is a privileged moiety with a wide range of bioactivities, making it a popular scaffold in drug design and development studies as well as in synthetic chemistry.Here, novel urea derivatives of indole, containing sulfonamide at position-3 of indole, were synthesized using a well-known tail approach, as carbonic anhydrases (CAs; EC 4.2.1.1) inhibitors. All the newly synthesized molecules were screened for their CA-inhibitory activity against four clinically relevant isoforms of human-origin carbonic anhydrase (hCA), that is, hCA I, hCA II, hCA IX, and hCA XII. These compounds were specifically active against hCA II, more than against hCA I, hCA IX, and hCA XII. Derivative 6l was found to be most active, with a K i value of 7.7 µM against hCA II.

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Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

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confidence: 99%

Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors

Singh

Choli

Swain

et al. 2021

Archiv der Pharmazie

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

Section: Introductionmentioning

confidence: 99%

“…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.…”

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confidence: 99%

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

Osmaniye

Türkeş

Demir

et al. 2022

Archiv der Pharmazie

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Carbonic anhydrase (CA) enzymes are involved in many physiological events. These enzymes, which contain Zn 2+ in their structure, can be easily inhibited by dithiocarbamate compounds. In addition, CA enzyme inhibitory activities are known in groups such as sulfonamide and methylsulfonyl. For this purpose, in this study, a series of 23 new dithiocarbamate-methylsulfonyl derivatives were synthesized and their CA enzyme inhibitory activities were investigated. The inhibition potentials of the obtained compounds against the human CA I and CA II enzymes were investigated by the in vitro enzyme isolation method. It is seen that the compounds show activity at the nanomolar level. Molecular docking studies of the compounds were carried out by in silico methods. The poses of compounds 2a, 2e, 2o, and 2t are presented.

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“…Among all families only the α‐CAs class which is present in human and a total of 16 isozymes have been determined as members of the α‐CA family in mammals represented by human carbonic anhydrase (hCA) varies from hCA I to hCA XV. Out of these total 16 hCA isoforms, CAs I, II, III, VII, and XIII are cytosolic isoenzymes,CAs VA and VB are localized in the mitochondria,CA VI is a unique secreted isozyme, CAs IX, XII, and XIV are transmembrane proteins,and CAs IV and XV are GPI‐anchored to the cell membrane [6–8] …”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Discovery of a novel series of indolylchalcone-benzenesulfonamide hybrids acting as selective carbonic anhydrase II inhibitors

Cited by 11 publications

References 35 publications

Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors

Design and development of novel series of indole‐3‐sulfonamide ureido derivatives as selective carbonic anhydrase II inhibitors

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

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

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