2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site

Bozdağ, Murat; Supuran, Claudiu T.; Esposito, Davide; Carta, Fabrizio; Monti, Simona Maria; Simone, Giuseppina De; Alterio, Vincenzo

doi:10.1039/d0cc02857f

Cited by 8 publications

(6 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result confirms the importance of C3-deprotonation for metal ion coordination by these ligands. It is worth noting that despite the previous report of 1 as a hCAII inhibitor, 15 compound 1 was not active under the assay conditions used in the present study (which are not the same as the prior report).…”

contrasting

confidence: 76%

“…Among them, 1 (benzo[ d ]oxazole-2-(3H)-thione) was reported as an hCA inhibitor. 15 The metal-binding mode of 1 to the hCA active site was elucidated by protein crystallography and its activity against different hCA isoforms suggested the possibility of developing selective hCA inhibitors. Compounds 9 and 10 were also studied here, as they have been reported as thione-based MBPs for metalloenzyme inhibitors.…”

mentioning

confidence: 99%

“…Both hCAII and MMP-2 contain a catalytic Zn( ii ) ion coordinated by three histidine residues and a water molecule in a tetrahedral geometry. 26,27 Compounds 1 ( K i = 0.97 μM) 15 and 11 ( K i = 0.63 μM) 6 are known inhibitors of hCAII. Compounds 9 and 10 are known inhibitors for MMP-2 (IC 50 = 60 and 140 μM, respectively).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs

et al. 2023

View full text Add to dashboard Cite

show abstract

contrasting

confidence: 76%

mentioning

confidence: 99%

See 1 more Smart Citation

Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Benzothiazole and its related heterocycle benzoxazole are other versatile scaffolds in organic chemistry [ 24 , 25 ]. Their derivatives possess various biological activities, including anti-inflammatory, antitubercular, antifungal, and anti-diabetic properties [ 25 , 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties—Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities

et al. 2023

View full text Add to dashboard Cite

In the search for new bioactive compounds, a methodology based on combining two molecules with biological properties into a new hybrid molecule was used to design and synthesize of a series of ten indole derivatives bearing imidazole, benzothiazole-2-thione, or benzoxazole-2-thione moieties at the C-3 position. The compounds were spectroscopically characterized and tested for their antioxidant, antibacterial, and fungicidal activities. The crystal structures were determined for five of them. Comparison of the closely related structures containing either benzothiazole-2-thione or benzoxazole-2-thione clearly shows that the replacement of -S- and -O- ring atoms modify molecular conformation in the crystal, changes intermolecular interactions, and has a severe impact on biological activity. The results indicate that indole-imidazole derivatives with alkyl substituent exhibit an excellent cytoprotective effect against AAPH-induced oxidative hemolysis and act as effective ferrous ion chelating agents. The indole-imidazole compound with chlorine atoms inhibited the growth of fungal strains: Coriolus versicolor (Cv), Poria placenta (Pp), Coniophora puteana (Cp), and Gloeophyllum trabeum (Gt). The indole-imidazole derivatives showed the highest antibacterial activity, for which the largest growth-inhibition zones were noted in M. luteus and P. fluorescens cultures. The obtained results may be helpful in the development of selective indole derivatives as effective antioxidants and/or antimicrobial agents.

show abstract

“…Their abnormal levels result in glaucoma and edema. Many CA inhibitors (CAIs) mostly belong to the sulfonamide class such as benzimidazole-6-sulfonamides, acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, benzenesulfonamide, and so forth. − …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors

et al. 2021

View full text Add to dashboard Cite

This research reports the synthesis of new benzimidazole-derived N -acylhydrazones (NAH), their characterization using various spectroscopic methods, and in vitro evaluation as potent carbonic anhydrase-II inhibitors. Among the target compounds ( 9–29 ), few showed higher inhibition than the standard acetazolamide (IC 50 : 18.6 ± 0.43 μM), for example, compound 9 (IC 50 : 13.3 ± 1.25 μM), 10 (IC 50 : 17.2 ± 1.24 μM), 12 (IC 50 : 14.6 ± 0.62 μM), and 15 (IC 50 : 14.5 ± 1.05 μM). Molecular docking was performed on the most active compounds, which revealed their binding interactions with the active site of the enzyme, thus supporting the experimental findings.

show abstract

2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site

Abstract: 2-Mercaptobenzoxazole represents an interesting lead compound alternative to the classical sulfonamides for the development of selective carbonic anhydrase inhibitors.

Cited by 8 publications

References 37 publications

Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs

Masking thiol reactivity with thioamide, thiourea, and thiocarbamate-based MBPs

Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties—Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities

Synthesis, Bioactivity Assessment, and Molecular Docking of Non-sulfonamide Benzimidazole-Derived N-Acylhydrazone Scaffolds as Carbonic Anhydrase-II Inhibitors

Contact Info

Product

Resources

About