Sulfonamide diuretic azosemide as an efficient carbonic anhydrase inhibitor

Ferraroni, Marta; Angeli, Andrea; Pinteala, Mariana; Supuran, Claudiu T.

doi:10.1016/j.molstruc.2022.133672

Cited by 13 publications

(11 citation statements)

References 37 publications

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“…Sulfonamides are mainly used in the medical field as antibacterial agents, in addition to antibiotics, anti-inflammatory agents, antiviral agents, − anticancer agents, − oxytocin, butyryl cholinesterase inhibitors with anti-Alzheimer’s activity, diuretics, etc. In the field of plants, pyrabactin is the first synthetic sulfonamide-based agonist with an ABA-related effect.…”

Section: Resultsmentioning

confidence: 99%

Plant Regulation Functions of Novel Phthalimide Compounds Based on AtPYL2

Mei

Zhang

Zhao

et al. 2023

J. Agric. Food Chem.

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Novel agents contain the structure of phthalimide, which has antibacterial, insecticidal, and herbicidal activities. Recently, studies reported that these compounds can bind to plant hormone receptors and play important regulatory roles. In this study, the functions of agents were studied with in vitro and in vivo assays. The abscisic acid (ABA) receptor pyrabactin resistant-like 2 (PYL2) protein in Arabidopsis thaliana was expressed, purified, and crystallized; the analysis results of the crystal structure showed three AtPYL2 subunits in each asymmetric unit. The affinity of compounds Z1−Z11 to the AtPYL2 protein was tested by microscale thermophoresis (MST) and then verified by isothermal titration calorimetry (ITC). Furthermore, the binding pockets were found using molecular docking to verify the target relationships. Relevant in vivo assays for seed germination and a root growth assay were conducted, with the plant samples being treated with target compounds. The results show that the compounds Z3, Z5, and Z10 target AtPYL2 and that the dissociation constants for binding by MST were 3.59, 3.54, and 3.97 μmol/L, respectively, among them, and the molecular docking results showed that compounds Z3, Z5, and Z10 formed hydrophobic interactions with amino acid residues through hydrogen or halogen bonding. This highlights their potential as an ABA receptor protein agonist. On the other hand, in vivo, compounds Z3, Z5, and Z10 had different inhibitory effects on seed germination, with compound Z5 inhibiting the root growth of A. thaliana and compound Z10 affecting root growth. In conclusion, these compounds could regulate plant growth and could be further developed as new plant-regulating agents.

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Section: Resultsmentioning

confidence: 99%

Plant Regulation Functions of Novel Phthalimide Compounds Based on AtPYL2

Mei

Zhang

Zhao

et al. 2023

J. Agric. Food Chem.

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“…Aiming to produce new derivatives in light of all of the above, our current work was a continuation of our earlier investigation into N -heterocycle systems − and as part of our interest in the field of physiologically active chemicals, − with a focus on carbonic anhydrase inhibitors. ,,,− The synthesis, structure, and evaluation of several novel dihydro-pyrrol-2-one derivatives as inhibitors of tumor-associated human CA are thus reported here.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety

Al-Matarneh,

Pinteala,

Nicolescu

et al. 2024

J. Med. Chem.

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New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure− reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (K I 3.9−870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (K I 1.9−211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

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“…CAs are well known drug targets for the management of human diseases 12–15 , with their inhibitors acting as diuretics 16 , antiepileptics 17 , antiglaucoma 18 , antiobesity 19 and antitumor agents 20 . In the last decade, CAs from pathogens started to be considered as possible targets for the development of antiinfectives, for the management of diseases provoked by bacteria 21 , fungi 22 , protozoa 23 and worms 10 , 11 , 24 .…”

Section: Introductionmentioning

confidence: 99%

Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris

Aspatwar

Bonardi

Aisala

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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A β-class carbonic anhydrase (CA, EC 4.2.1.1) present in the genome of the Monogenean platyhelminth Gyrodactylus salaris, a fish parasite, GsaCAβ, has been investigated for its inhibitory effects with a panel of sulphonamides and sulfamates, some of which in clinical use. Several effective GsaCAβ inhibitors were identified, belonging to simple heterocyclic sulphonamides, the deacetylated precursors of acetazolamide and methazolamide ( K I sof 81.9–139.7 nM). Many other simple benezene sulphonamides and clinically used agents, such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, benzolamide, sulthiame and hydrochlorothiazide showed inhibition constants <1 µM. The least effective GsaCAβ inhibitors were 4,6-disubstituted-1,3-benzene disulfonamides, with K I s in the range of 16.9–24.8 µM. Although no potent GsaCAβ-selective inhibitors were detected so far, this preliminary investigation may be helpful for better understanding the inhibition profile of this parasite enzyme and for the potential development of more effective and eventually parasite-selective inhibitors.

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Sulfonamide diuretic azosemide as an efficient carbonic anhydrase inhibitor

Cited by 13 publications

References 37 publications

Plant Regulation Functions of Novel Phthalimide Compounds Based on AtPYL2

Plant Regulation Functions of Novel Phthalimide Compounds Based on AtPYL2

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety

Sulphonamide inhibition studies of the β-carbonic anhydrase GsaCAβ present in the salmon platyhelminth parasite Gyrodactylus salaris

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