Derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide as selective inhibitors of human carbonic anhydrases IX and XII over the cytosolic isoforms I and II

Ivanova, Jekaterīna; Abdoli, Morteza; Nocentini, Alessio; Žalubovskis, Raivis; Supuran, Claudiu T.

doi:10.1080/14756366.2023.2170370

Cited by 8 publications

(1 citation statement)

References 62 publications

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“…In this context, over the last decade, several research groups have disclosed that sulfonamide–acyl thiourea derivatives were effective inhibitors of CAs ( Figure 1 b) [ 12 , 13 , 14 , 15 , 16 ]. In order to extend these efforts and in continuation of our interest in the study of sulfonamide CAIs [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], in the present study, we synthesized a panel of 12 structurally diverse N -((4-sulfamoylphenyl)carbamothioyl) amides by the reaction of easily available 4-thioureidobenzenesulfonamide with the appropriate acid chlorides and investigated their inhibitory activities against three human CAs (hCA I, hCA II and hCA VII) and three bacterial β-CAs from Mycobacterium tuberculosis (MtCA1-MtCA3), which were recently validated as effective targets for the development of antituberculosis agents [ 37 , 38 , 39 , 40 , 41 , 42 , 43 ], to discover possible promising drug candidate(s).…”

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confidence: 99%

Inhibition Studies on Human and Mycobacterial Carbonic Anhydrases with N-((4-Sulfamoylphenyl)carbamothioyl) Amides

et al. 2023

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A library of structurally diverse N-((4-sulfamoylphenyl)carbamothioyl) amides was synthesized by selective acylation of easily accessible 4-thioureidobenzenesulfonamide with various aliphatic, benzylic, vinylic and aromatic acyl chlorides under mild conditions. Inhibition of three α-class cytosolic human (h) carbonic anhydrases (CAs) (EC 4.2.1.1); that is, hCA I, hCA II and hCA VII and three bacterial β-CAs from Mycobacterium tuberculosis (MtCA1-MtCA3) with these sulfonamides was thereafter investigated in vitro and in silico. Many of the evaluated compounds displayed better inhibition against hCA I (KI = 13.3–87.6 nM), hCA II (KI = 5.3–384.3 nM), and hCA VII (KI = 1.1–13.5 nM) compared with acetazolamide (AAZ) as the control drug (KI values of 250, 12.5 and 2.5 nM, respectively, against hCA I, hCA II and hCA VII). The mycobacterial enzymes MtCA1 and MtCA2 were also effectively inhibited by these compounds. MtCA3 was, on the other hand, poorly inhibited by the sulfonamides reported here. The most sensitive mycobacterial enzyme to these inhibitors was MtCA2 in which 10 of the 12 evaluated compounds showed KIs (KI, the inhibitor constant) in the low nanomolar range.

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Section: Introductionmentioning

confidence: 99%

Inhibition Studies on Human and Mycobacterial Carbonic Anhydrases with N-((4-Sulfamoylphenyl)carbamothioyl) Amides

et al. 2023

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Sulfonamide‐incorporated bis(α‐aminophosphonates) as promising carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and X‐ray crystallographic studies

Sobati,

Abdoli,

Angeli

et al. 2024

Archiv der Pharmazie

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A novel series of sulfonamide‐incorporated bis(α‐aminophosphonates) acting as effective carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. The synthesized bivalent ligands were tested against five human (h) isoforms, hCA I, hCA II, hCA VII, hCA IX, and hCA XIII. Such derivatives showed high activity and selectivity against the cancer‐related, membrane‐bound isoform hCA IX, and among them, compound 5h, tetraisopropyl (1,3‐phenylenebis{[(4‐sulfamoylphenyl)amino]methylene})bis(phosphonate) showed a KI of 15.1 nM, being highly selective against this isoform over all other investigated ones (hCA I/IX = 42; hCA II/IX = 6, hCA VII/IX = 3, hCA XIII/IX = 5). Therefore, compound 5h could be a potential lead for the development of selective anticancer agents. The newly developed sulfonamides were also found effective inhibitors against the cytosolic hCA XIII isoform. Compound 5i displayed the best inhibition against this isoform with a KI of 17.2 nM, equal to that of the well‐known inhibitor acetazolamide (AAZ), but significantly more selective over all other tested isoforms (hCA I/XIII = 239; hCA II/XIII = 23, hCA VII/XIII = 2, hCA IX/XIII = 3) compared to AAZ.

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Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

Bendi,

Taruna,

Rajni

et al. 2024

Archiv der Pharmazie

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Nowadays, the scientific community has focused on dealing with different kinds of diseases by exploring the chemistry of various heterocycles as novel drugs. In this connection, medicinal chemists identified carbonic anhydrases (CA) as one of the biologically active targets for curing various diseases. The widespread distribution of these enzymes and the high degree of homology shared by the different isoforms offer substantial challenges to discovering potential drugs. Medicinal and synthetic organic chemists have been continuously involved in developing CA inhibitors. This review explored the chemistry of different heterocycles as CA inhibitors using the last 11 years of published research work. It provides a pathway for young researchers to further explore the chemistry of a variety of synthetic as well as natural heterocycles as CA inhibitors.

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Derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide as selective inhibitors of human carbonic anhydrases IX and XII over the cytosolic isoforms I and II

Cited by 8 publications

References 62 publications

Inhibition Studies on Human and Mycobacterial Carbonic Anhydrases with N-((4-Sulfamoylphenyl)carbamothioyl) Amides

Inhibition Studies on Human and Mycobacterial Carbonic Anhydrases with N-((4-Sulfamoylphenyl)carbamothioyl) Amides

Sulfonamide‐incorporated bis(α‐aminophosphonates) as promising carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and X‐ray crystallographic studies

Chemistry of heterocycles as carbonic anhydrase inhibitors: A pathway to novel research in medicinal chemistry review

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