Sulfamide derivatives with selective carbonic anhydrase VII inhibitory action

Villalba, María Luisa; Palestro, Pablo Hernán; Ceruso, Mariangela; Funes, Jose L. Gonzalez; Talevi, Alan; Blanch, Luis Bruno; Supuran, Claudiu T.; Gavernet, Luciana

doi:10.1016/j.bmc.2016.01.012

Cited by 22 publications

(17 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To date, this animal model has provided new opportunities to examine how this neuron-specific isoform modulates excitability. Currently, the main scope is to design, synthesize and evaluate new carbonic anhydrase-VII inhibitors [236,237]. In this sense, De Luca et al [238] performed a virtual screening to find such compounds.…”

Section: Carbonic Anhydrase Seizures and Epilepsymentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

View full text Add to dashboard Cite

Epilepsy is a chronic brain disease that affects approximately 65 million people worldwide. However, despite the continuous development of antiepileptic drugs, over 30% patients with epilepsy progress to drug-resistant epilepsy. For this reason, it is a high priority objective in preclinical research to find novel therapeutic targets and to develop effective drugs that prevent or reverse the molecular mechanisms underlying epilepsy progression. Among these potential therapeutic targets, we highlight currently available information involving signaling pathways (Wnt/β-catenin, Mammalian Target of Rapamycin (mTOR) signaling and zinc signaling), enzymes (carbonic anhydrase), proteins (erythropoietin, copine 6 and complement system), channels (Transient Receptor Potential Vanilloid Type 1 (TRPV1) channel) and receptors (galanin and melatonin receptors). All of them have demonstrated a certain degree of efficacy not only in controlling seizures but also in displaying neuroprotective activity and in modifying the progression of epilepsy. Although some research with these specific targets has been done in relation with epilepsy, they have not been fully explored as potential therapeutic targets that could help address the unsolved issue of drug-resistant epilepsy and develop new antiseizure therapies for the treatment of epilepsy.

show abstract

Section: Carbonic Anhydrase Seizures and Epilepsymentioning

confidence: 99%

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Zavala-Tecuapetla

Cuéllar-Herrera

Luna-Munguía

2020

IJMS

View full text Add to dashboard Cite

show abstract

“…4.4 | CA VII-selective inhibitorsAs discussed above, CA VII is widely expressed in several regions of the brain and validated as a promising target for epilepsy 136. Additionally, Parkkila's group recently observed elevated expression of this isoform in brain tumor This compound has shown >256 41-, 25 641-, 490-, 86-, and 20-fold selectivity for hCA VII over hCA I, hCA II, hCA IX, hCA XII, and hCA XIV, respectively 259. Mishra et al have also designed and synthesized benzenesulfonamide-piperazine hybrid molecules as potent hCAs inhibitors and some of them like piperonyl containing benzenesulfonamide (compound 175,Figure 14)indicated low nanomolar range inhibitory action (K i = 4 nM) against hCA VII, showing promising selectivity over hCA I, hCA II, and hCA XII.…”

mentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

Self Cite

179

166

View full text Add to dashboard Cite

Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

show abstract

“…Among top scoring hits, 10 structures were selected for biological evaluation. All the candidates were tested before as human CA II inhibitors and they showed poor inhibitory potency in this mammalian isoform [46][47][48] . As previously mentioned, CA II is ubiquitous in humans and it was considered as an antitarget in this investigation, since we are looking for selective inhibitors of the parasite isoform.…”

Section: Virtual Screeningmentioning

confidence: 99%

“…The biological results against TcCA of this family would give us the opportunity to get information about the structure-activity relationships. The set was completed with two artificial sweeteners, acesulphame and sodium cyclamate, which also have low potency as human CA II inhibitors and different scaffolds than the other selected candidates 47,48 . Additionally, they are commercially available compounds approved for human consumption.…”

Section: Validation Of the Docking Protocol For Tcca Virtual Screeningmentioning

confidence: 99%

A structure-based approach towards the identification of novel antichagasic compounds: Trypanosoma cruzi carbonic anhydrase inhibitors

Llanos

Sbaraglini

Villalba

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Trypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with KI values in the nanomolar range. The compounds also showed trypanocidal effects against T. cruzi epimastigotes and trypomastigotes. All the candidates are selective for inhibiting TcCA over the human isoform CA II, which is encouraging in terms of possible therapeutic safety and efficacy.

show abstract

Sulfamide derivatives with selective carbonic anhydrase VII inhibitory action

Cited by 22 publications

References 58 publications

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Insights into Potential Targets for Therapeutic Intervention in Epilepsy

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

A structure-based approach towards the identification of novel antichagasic compounds: Trypanosoma cruzi carbonic anhydrase inhibitors

Contact Info

Product

Resources

About