HCO₃^- is involved in pH homoeostasis and plays a multifaceted role in human health. HCO₃^- has been recognized for its antimicrobial properties and is pivotal in bacterial antibiotic susceptibility. Notably, the interconversion between CO₂ and HCO₃^-, facilitated by the enzyme carbonic anhydrase (CA), is crucial in tissues infected by pathogens. Studies have highlighted the antimicrobial potency of CA inhibitors, emphasizing the importance of this enzyme in this area. The potential of HCO₃^- as an antibiotic adjuvant is evident; its ability to increase virulence in pathogens such as Enterococcus faecalis and Mycobacterium tuberculosis requires meticulous scrutiny. HCO₃^- modulates bacterial behaviours in diverse manners: it promotes Escherichia coli O157:H7 colonization in the human gut by altering specific gene expression and, with Pseudomonas aeruginosa, amplifies the effect of tobramycin on planktonic cells while promoting biofilm formation. These multifaceted effects necessitate profound mechanistic exploration before HCO₃^- can be considered a promising clinical adjuvant.

01 Jul 2025·European Journal of Medicinal Chemistry

Redesigning oxazolidinones as carbonic anhydrase inhibitors against vancomycin-resistant enterococci

Article

Author: Ammara, Andrea ; Abouelkhair, Ahmed A ; Bonardi, Alessandro ; Capasso, Clemente ; Gratteri, Paola ; Seleem, Mohamed N ; Supuran, Claudiu T ; Flaherty, Daniel P ; Nocentini, Alessio ; Abutaleb, Nader S ; Giovannuzzi, Simone

The rise of vancomycin-resistant enterococci (VRE) as a leading cause of hospital-acquired infections underscores the urgent need for new treatment strategies. In fact, resistance has developed not only to vancomycin but also to other clinically used agents, such as daptomycin and linezolid. We propose a novel drug design approach merging tedizolid, a second-generation oxazolidinone used as an unapproved salvage therapy in clinical settings, with carbonic anhydrase inhibitors (CAIs) recently validated as functioning decolonization agents. These sulfonamide derivatives showed potent inhibition of the carbonic anhydrases from Enterococcus faecium, with K_I values in the range of 14.6-598 nM and 63.2-798 nM against EfCAα and EfCAγ. Computational simulations elucidated the binding mode of these dual-action antibiotics to the peptidyl transferase center (PTC) of the 50S ribosome subunit and bacterial CAs. A subset of six derivatives showed potent PTC-related anti-enterococcal effects against multidrug-resistant E. faecalis and E. faecium strains with some compounds outperforming both the oxazolidinone and CA inhibitor drugs (MIC values in the range 1-4 μg/mL).

01 May 2025·Bioactive Materials

Self-healable and pH-responsive spermidine/ferrous ion complexed hydrogel Co-loaded with CA inhibitor and glucose oxidase for combined cancer immunotherapy through triple ferroptosis mechanism

Article

Author: Wu, Jun ; Zhang, Ruhe ; Cai, Yishui ; Fang, Yifei ; Jiao, Yuenong ; Wang, Xiaobo ; Nie, Tianqi

Tumor microenvironment governs various therapeutic tolerability of cancer such as ferroptosis and immunotherapy through rewiring tumor metabolic reprogramming like Warburg metabolism. Highly expressed carbonic anhydrases (CA) in tumor that maintaining the delicate metabolic homeostasis is thus the most potential target to be modulated to resolve the therapeutic tolerability. Hence, in this article, a self-healable and pH-responsive spermidine/ferrous ion hydrogel loaded with CA inhibitor (acetazolamide, ACZ) and glucose oxidase (ACZ/GOx@SPM-HA Gel) was fabricated through the Schiff-base reaction between spermidine-dextran and oxidized hyaluronic acid, along with ferrous coordination. Investigation on cancer cell lines (MOC-1) demonstrated ACZ/GOx@SPM-HA Gel may induce cellular oxidative stress and mitochondrial dysfunction through disrupting the cellular homeostasis. Moreover, with the facilitation of autophagy induced by spermidine, ACZ/GOx@SPM-HA Gel may trigger a positive feedback loop to maximally amplify cellular ferroptosis and promote DAMPs release. The anti-tumor evaluation on xenograft mice models furtherly proved the local injection of such hydrogel formulation could efficiently inhibit the tumor growth and distinctively promote the immunogenicity of tumor bed to provide a more favorable environment for immunotherapy. Overall, ACZ/GOx@SPM-HA Gel, with such feasible physiochemical properties and great biocompatibility, holds great potential in treating solid tumors with acidosis-mediated immunotherapy tolerance.

100 Deals associated with CA inhibitor (Sakarya University)

R&D Status

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

CA inhibitor (Sakarya University)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation