Two series of sulfonamide derivatives featuring a pyrrol-2-one core were synthesized and evaluated for their antimicrobial and anti-virulence features using Escherichia coli , Pseudomonas aeruginosa , and Candida albicans strains, in planktonic and biofilm growth state. Fourteen substituents were introduced on the pyrrole ring, and the sulfonamide group was shifted from meta - (Series B) to para -position (Series A). Meta -substituted sulfonamides generally exhibited stronger antibacterial activity, likely via selective inhibition of microbial β -/ γ -class carbonic anhydrases, while para -substituted derivatives demonstrated superior antifungal activity and antibiofilm potential. Also, series A compounds were particularly effective in inhibiting virulence factors, including haemolysin ( S. aureus ), lipase and acidification ( C. albicans ), and lecithinase ( P. aeruginosa ). Structure–activity relationships revealed that para -substitution aligns with human CA II, correlated with an enhanced antifungal efficacy, whereas meta -substitution favors microbial CA targeting, explaining antibacterial selectivity. Antimicrobial efficacy correlated weakly with lipophilicity and solubility, underscoring species-specific activity. Lipophilicity increased skin permeability but decreased solubility, negatively affecting biocompatibility. However, none of the tested compounds were haemolytic at 1 mg/mL, and all were well tolerated by dermal fibroblasts and keratinocytes at 10 µM. Collectively, these results highlight the dual functionality of these derivatives as selective anti-virulence and antimicrobial agents, while their skin-friendly properties make them promising candidates for the treatment of dermal infections.

Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein-protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms.

Nanoplastic exposure induces exoskeletal misdevelopment in juvenile Tachypleus tridentatus: Compensatory hardening versus molecular suppression.

High-efficiency restoration of stone cultural relics via immobilized carbonic anhydrase on magnetic graphite oxide.

LC-MS/MS characterization, biological activity, and carbonic anhydrase inhibitory potential of five medicinal plant extracts from Romania and Türkiye.

Acetylcholinesterase (AChE) is one of the most important therapeutic targets in the treatment of neurological disorders such as Alzheimer's disease. In recent years, studies on the use of carbonic anhydrase (CA) inhibitors in the treatment of Alzheimer's disease have attracted considerable attention. In this study, novel benzene/5-HMF-chalcone hybrids and their benzoate esters were synthesized. Furthermore, the AChE, carbonic anhydrases I and II (CA I and II) inhibition potentials of the compounds were evaluated through in vitro enzyme inhibition assays and molecular docking studies to identify new potential drug candidate molecules. According to the inhibition results, the Ki values of the synthesized compounds were found to be in the range of 1.51-2.91 nM against AChE, 26.15-68.66 nM against CA I, and 27.91-107.04 nM against CA II. Molecular docking studies revealed that the compounds bind to both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE, with Glide scores ranging from -5.76 to -8.50 kcal/mol. In contrast, the molecules interacted with the active site of CA I/II by coordinating with the catalytic Zn2+ ion. All compounds complied with Lipinski's Rule of Five, indicating favorable drug-like properties. These results suggest that 5-HMF-chalcone hybrids and their benzoate derivatives could serve as promising scaffolds for the development of new anti-Alzheimer's agents. These findings suggest that 5-HMF-chalcone hybrids and their benzoate derivatives may be useful in establishing the structural basis of new anti-Alzheimer's agents.

Exploring dual inhibitors Carbonic Anhydrases and Phosphodiesterase 5 as potential agents for treatment Alzheimer's disease.

Structure-based drug design; Computational strategies in drug discovery; Antihypertensive agents; Antiviral drugs; Molecular docking; QSAR; Pharmacological insights.

Impact of acidification and ultraviolet radiation on the physiology of Ulva fasciata.

The study of complex proteoforms with mutations and post-translational modifications has gained increasing attention with the advancement of mass spectrometry (MS)-based techniques. Achieving high proteoform sequence coverage by MS is essential for accurately characterizing these complex proteoforms. Extensive efforts have been made to increase the proteoform sequence coverage using deep bottom-up and top-down MS strategies. In this study, we evaluated top-down and middle-down MS approaches for enhancing proteoform sequence coverage using three proteins: ubiquitin, myoglobin, and carbonic anhydrase II. In the top-down MS approach, we applied in-source fragmentation (ISF) to generate pseudo-MS3 spectra, thereby improving sequence coverage. For the middle-down MS strategy, we performed short-duration enzymatic digestions to produce longer peptides that preserve more proteoform sequence information. Our experimental results demonstrated that ISF and partial digestion significantly increased the sequence coverage of the proteins, achieving coverage greater than 90%.

Beyond zinc porphyrins: Immobilized algal chlorophyllin carboxylates as hydrophilic carbonic anhydrase mimics for recyclable CO2 capture

Genome-wide identification, functions, and expression analysis of carbonic anhydrase gene family in the gills of O. niloticus under salinity stress

Ketoconazole-carbonic anhydrase inhibitors as potential anticancer agents.

We demonstrate triblock polyelectrolyte complex (PEC) hydrogels as a model platform for protein delivery and unveil their precisely tunable swelling behaviors. PEC hydrogels self-assemble in water, do not require UV light or organic solvents, and demonstrate easily tunable shear properties. However, for PEC hydrogels to be effectively designed as protein delivery vehicles, it is imperative to understand the influence of protein additives on their microstructure and swelling behavior. Herein, we utilize small-angle X-ray scattering to demonstrate that model proteins, including bovine serum albumin, lipase, human carbonic anhydrase II, and urease, do not perturb the PEC hydrogel microstructure at therapeutically relevant concentrations. The swelling and dissolution characteristics are shown to be precisely controlled by triblock polyelectrolyte (tbPE) end-block length and concentration. Moreover, we demonstrate that PEC hydrogel swelling and dissolution characteristics, as well as their shear moduli, are unaffected by protein inclusion. Finally, we demonstrate tunable protein release in PEC hydrogels by varying tbPE concentration and end-block length, mixing tbPEs of different lengths to create mixed PEC hydrogels, and incorporating a covalent interpenetrated network. Our work provides easily accessible design parameters to achieve the desired protein release characteristics in PEC hydrogels. At the same time, it also provides insights into the influence of charged macromolecules on the microstructure and dynamics of PEC-based self-assemblies.

Leukemia remains a challenging hematological malignancy, with limited therapeutic options. To address this unmet need, we report quinoline-sulfonamide hybrids as first-in-class dual inhibitors of platelet-derived growth factor receptor (PDGFR) and carbonic anhydrase (CA) IX/XII. Structure-activity relationship studies identified compound 9d as a potent lead, exhibiting strong inhibition of PDGFRA (IC50 = 20 nM) and CA IX/XII (KI = 93.3 and 80.0 nM, respectively), along with exceptional antiproliferative activity in FIP1L1-PDGFRA-driven EOL-1 cells (GI50 = 2 nM), comparable to clinical agents. Mechanistic analyses revealed that 9d effectively abrogates PDGFRA signaling, induces G0/G1 cell-cycle arrest, and triggers apoptosis. Molecular docking and 200 ns molecular dynamics simulations supported stable dual binding of 9d within the ATP-binding pocket of PDGFR and the catalytic cleft of CA IX. By simultaneously targeting oncogenic PDGFRA signaling and hypoxia-driven pH regulation (CA IX/XII), 9d represents a promising lead for preclinical development in PDGFR/CA IX/XII-driven leukemias.

Bio-based carbon capture, utilization and storage (CCUS) presents a promising alternative to conventional CCU methods, primarily due to its inherent potential for valorization. In the present study, carbonic anhydrase extracted from spinach leaves (Spinacia oleracea) was immobilized onto citric acid-functionalized magnetite nanoparticles (Fe3O4@CA NPs). This bio-nano hybrid functions as an efficient catalyst for enhancing CO2 solubility by accelerating its conversion to bicarbonate (HCO3⁻), thereby overcoming the low aqueous solubility of gaseous CO2, a known limiting factor in photosynthetic autotrophs. Growth experiments using Escherichia coli cultures supplemented with these NPs demonstrated a ~62% increase in biomass production compared to the control group when the culture was sparged with atmospheric air, demonstrating that carbonic anhydrase-immobilized NPs effectively facilitated the uptake of atmospheric CO2 and redirected it into cellular biomass. Considering that 1 g E. coli dry cell weight can capture ~86 mg CO2, this approach can be used for carbon capture and production of fermentation-derived value-added products. Moreover, such systems hold significant potential for applications in algal biofuel production and the cultivation of slow-growing organisms, such as cyanobacteria, where efficient carbon assimilation is crucial for their growth.

Valproic acid (VPA) is a short-chain fatty acid used to treat disorders of the brain. When VPA is used for long term, it causes damage, particularly through the formation of free radicals. The lungs are among the organs most affected by long-term VPA treatment. Some antioxidant substances are used to prevent damage caused by free radicals. One of these substances is alpha-lipoic acid (ALA), which occurs naturally. In our study, the protective effect of ALA against VPA-induced lung injury was investigated. In this study, female Sprague-Dawley rats were divided into four groups. The 1st group served as the control (1 mL olive oil); the 2nd group received ALA (50 mg/kg/day) for 15 days; the 3rd group received VPA (0.5 g/kg/day) for 15 days; and the 4th group received both VPA and ALA at the same doses and for the same duration. ALA and VPA were dissolved in olive oil. On day 16, all groups were euthanized under anesthesia. The lung tissues were collected and homogenized. In the prepared supernatants, the levels of reduced glutathione and total antioxidant status, and the activities of glutathione reductase, glutathione peroxidase, catalase, paraoxonase, carbonic anhydrase, aryl esterase, and superoxide dismutase were decreased in the VPA group, while sialic acid, lipid peroxidation, reactive oxygen species, total oxidant, oxidative stress index, hydroxyproline, glycoprotein levels, and xanthine oxidase activities were increased in the VPA group. These values were reversed in ALA when VPA was administered. As a result, it may be concluded that ALA exerts protective effects against VPA-induced lung damage.

From Carbonic Anhydrase 12 to TGFβ1/Smad Pathway: A Key Mechanism for Isoorientin in Pulmonary Fibrosis Therapy.

Persistent vulnerability to drug-seeking is driven by enduring synaptic adaptations, yet current μ-opioid receptor-targeting pharmacotherapies provide limited efficacy against these neuroadaptations. Thus, there is a critical need for mechanistically distinct, non-opioid interventions. We recently found that carbonic anhydrase 4 (CA4) disruption reduces cocaine-induced synaptic adaptations and drug-seeking. Building on this foundation, we sought to determine whether deleting CA4 or pharmacological inhibition with acetazolamide (AZD), a clinically employed carbonic anhydrase inhibitor-could mitigate opioid withdrawal-associated plasticity and thus might reduce relapse vulnerability. We studied synaptic and behavioral adaptations to withdrawal from oxycodone in mice and found that prolonged withdrawal from oxycodone increased the AMPAR/NMDAR ratio and promoted synaptic incorporation of Ca2+-permeable AMPARs in nucleus accumbens core (NAcC) medium spiny neurons (MSNs). We found synaptic changes after protracted withdrawal from multiple opioids, which were most pronounced in D1-expressing MSNs, and were prevented by CA4 disruption. Moreover, AZD reversed withdrawal-induced synaptic alterations both in vitro and in vivo, in a CA4- and acid-sensing ion channel 1A (ASIC1A)-dependent manner. Unlike withdrawal from cocaine, withdrawal from oxycodone did not alter dendritic spine density in NAcC MSNs, suggesting a distinct mode of plasticity. Finally, following oxycodone self-administration, both CA4 deletion and a single systemic AZD dose reduced drug-seeking after prolonged abstinence. Together, these findings identify CA4 as a regulator of opioid-induced synaptic adaptations and suggest AZD as a promising, readily translatable pharmacological intervention. By targeting a pathway independent of classical opioid receptor signaling, CA4 inhibition represents a mechanistically distinct strategy that may reduce relapse vulnerability in OUD.

Glaucoma is a leading cause of irreversible blindness worldwide, characterized by optic nerve damage that is often associated with elevated intraocular pressure. Topical antiglaucoma medications, such as prostaglandin analogues, β-blockers, carbonic anhydrase inhibitors, α-adrenergic agonists, and Rho-kinase inhibitors, represent the mainstay of treatment; however, long-term therapy with these drugs is invariably associated with ADRs, including conjunctival hyperemia, ocular surface inflammation, Meibomian gland dysfunction, and tear film instability. These generally result from drug-induced structural and physiological changes in the conjunctiva, cornea, and tear film. In recent years, compelling evidence has emerged that supplementation with omega-3 fatty acids and hyaluronic acid can prevent and alleviate these ADRs. Omega-3 fatty acids suppress ocular surface inflammation, enhance tear film stability, and improve meibomian gland function, while HA enhances corneal healing, ocular surface lubrication, and epithelial regeneration. In addition, ocular barriers in the eye often impede the poor bioavailability of conventional topical medications, necessitating the development of NDDS. Nanoparticles, nanoemulsions, in-situ gels, and ocular inserts exhibit improved corneal permeability, prolonged retention time, and sustained drug release, thereby offering superior therapeutic outcomes with less local irritation. Combining omega-3 fatty acids and HA with NDDS may thus represent a new strategy to improve ocular drug delivery while minimizing ADRs associated with chronic antiglaucoma medications. This review highlights the mechanism underlying these side effects and discusses new opportunities to improve drug safety and compliance in long-term glaucoma management.