Identification, crystallization, and first X-ray structure analyses of phenyl boronic acid-based inhibitors of human carbonic anhydrase-II
In this study, different phenyl boronic acids 1-5 were evaluated against bovine (bCA II) and hCA II. Among all, compound 1 (4-acetylphenyl boronic acid) was found to be active against bCAII and hCA II with IC50 values of 246 ± 0.48 and 281.40 ± 2.8 μM, respectively, while the remaining compounds were found in-active. Compound 1 was identified as competitive inhibitor of hCA II enzyme (Ki = 283.7 ± 0.002 μM). Additionally, compound 1 was found to be non-toxic against BJ Human fibroblast cell line. The X-ray crystal structure for hCA II in-complex with compound 1 was evaluated to a resolution of 2.6 Å. In fact, this th...
Source: International Journal of Biological Macromolecules - April 5, 2024 Category: Biochemistry Authors: Saima Rasheed Noor Ul Huda S Zo ë Fisher Sven Falke Sadaf Gul Malik Shoaib Ahmed M Iqbal Choudhary Source Type: research
Exposure to topiramate and acetazolamide causes endocrine disrupting effects in female rats during estrus
CONCLUSION: These results demonstrate that both acetazolamide and topiramate have endocrine disrupting effects in rats. Topiramate primarily targeted the choroid plexus and the pituitary gland while acetazolamide had broader systemic effects. Furthermore, topiramate predominantly targeted sex hormones, whereas acetazolamide widely affected all classes of hormones. A similar effect in humans has not yet been documented but these concerning findings warrants further investigations.PMID:38580201 | DOI:10.1016/j.taap.2024.116919 (Source: Toxicology and Applied Pharmacology)
Source: Toxicology and Applied Pharmacology - April 5, 2024 Category: Toxicology Authors: Christina Kamp-Jensen Louise Norgil Donslund Bjarne Styrishave Rigmor H øjland Jensen Connar Stanley James Westgate Source Type: research
Combining BNCT with carbonic anhydrase inhibition for mesothelioma treatment: Synthesis, in vitro, in vivo studies of ureidosulfamido carboranes
Eur J Med Chem. 2024 Mar 26;270:116334. doi: 10.1016/j.ejmech.2024.116334. Online ahead of print.ABSTRACTMesothelioma is a malignant neoplasm of mesothelial cells caused by exposure to asbestos. The average survival time after diagnosis is usually nine/twelve months. A multi-therapeutic approach is therefore required to treat and prevent recurrence. Boronated derivatives containing a carborane cage, a sulfamido group and an ureido functionality (CA-USF) have been designed, synthesised and tested, in order to couple Boron Neutron Capture Therapy (BNCT) and the inhibition of Carbonic Anhydrases (CAs), which are overexpressed...
Source: European Journal of Medicinal Chemistry - March 29, 2024 Category: Chemistry Authors: Alberto Lanfranco Sahar Rakhshan Diego Alberti Polyssena Renzi Ayda Zarechian Nicoletta Protti Saverio Altieri Simonetta Geninatti Crich Annamaria Deagostino Source Type: research
Novel carbonic anhydrase inhibitors for the treatment of < em > Helicobacter pylori < /em > infection
Expert Opin Investig Drugs. 2024 Mar 22. doi: 10.1080/13543784.2024.2334714. Online ahead of print.ABSTRACTINTRODUCTION: Helicobacter pylori, the causative agent of peptic ulcer, gastritis and gastric cancer encodes two carbonic anhydrases (CA, EC 4.2.1.1) belonging to the α- and β-class (HpCAα/β), which have been validated as antibacterial drug targets. Acetazolamide and ethoxzolamide were also clinically used for the management of peptic ulcer.AREAS COVERED: Sulfonamides were the most investigated HpCAα/β compounds, with several low nanomolar inhibitors indentified, some of which also crystallized as adducts with H...
Source: Expert Opinion on Investigational Drugs - March 22, 2024 Category: Drugs & Pharmacology Authors: Claudiu T Supuran Source Type: research
Novel carbonic anhydrase inhibitors for the treatment of < em > Helicobacter pylori < /em > infection
Expert Opin Investig Drugs. 2024 Mar 27:1-10. doi: 10.1080/13543784.2024.2334714. Online ahead of print.ABSTRACTINTRODUCTION: Helicobacter pylori, the causative agent of peptic ulcer, gastritis, and gastric cancer encodes two carbonic anhydrases (CA, EC 4.2.1.1) belonging to the α- and β-class (HpCAα/β), which have been validated as antibacterial drug targets. Acetazolamide and ethoxzolamide were also clinically used for the management of peptic ulcer.AREAS COVERED: Sulfonamides were the most investigated HpCAα/β compounds, with several low nanomolar inhibitors identified, some of which also crystallized as adducts w...
Source: Expert Opinion on Investigational Drugs - March 22, 2024 Category: Drugs & Pharmacology Authors: Claudiu T Supuran Source Type: research
