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  1. Imran S, Taha M, Ismail NH, Fayyaz S, Khan KM, Choudhary MI
    Bioorg Chem, 2016 10;68:90-104.
    PMID: 27474804 DOI: 10.1016/j.bioorg.2016.07.011
    In this study, 45 bisindolylmethanes having sulfonamide moiety had been synthesized through 3 steps. In vitro assay for inhibition of carbonic anhydrase showed that some of the compounds having sulfonamide moiety are capable of inhibiting carbonic anhydrase II. Bisindoles having halogens at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. The results obtained from in vitro inhibitory activity were subjected through 3D QSAR and docking studies to identify important features contributing to the activity and further improve the structure. Pharmacophore studies suggest that bisindolylmethane moiety is contributing significantly towards the inhibition activity. Docking studies showed that compounds having nitro substituent (5g and 5i) were found to be able interact with Zn(2+) ion, Thr199, His94, His96, and His119, which interferes with the ZnOHThr199Glu106 hydrogen bond network. Bulky nitro substituent at ortho position for compound 5g prevents the compound from interacting with other residues like Thr199 and Thr200. Methyl substituent at ortho position for Compound 5i induces less steric hindrance effect, thus allowing second oxygen atom of sulfonamide to interact with Thr199 (2.51Å). Hydrogen bonding between NH on indole ring with Glu69 might have increased stability of ligand-receptor complex.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry
  2. Bozdag M, Alafeefy AM, Carta F, Ceruso M, Al-Tamimi AS, Al-Kahtani AA, et al.
    Bioorg Med Chem, 2016 09 15;24(18):4100-4107.
    PMID: 27396930 DOI: 10.1016/j.bmc.2016.06.052
    Condensation of substituted anthranilic acids with 4-isothiocyanatoethyl-benzenesulfonamide led to series of heterocyclic benzenesulfonamides incorporating 2-mercapto-quinazolin-4-one tails. These sulfonamides were investigated as inhibitors of the human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms hCA I and II (cytosolic isozymes), as well as hCA XII (a transmembrane, tumor-associated enzyme also involved in glaucoma-genesis). The new sulfonamides acted as medium potency inhibitors of hCA I (KIs of 28.5-2954nM), being highly effective as hCA II (KIs in the range of 0.62-12.4nM) and XII (KIs of 0.54-7.11nM) inhibitors. All substitution patterns present in these compounds (e.g., halogens, methyl and methoxy moieties, in positions 6, 7 and/or 8 of the 2-mercapto-quinazolin-4-one ring) led to highly effective hCA II/XII inhibitors. These compounds should thus be of interest as preclinical candidates in pathologies in which the activity of these enzymes should be inhibited, such as glaucoma (CA II and XII as targets) or some tumors in which the activity of isoforms CA II and XII is dysregulated.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry*
  3. Iqbal S, Saleem M, Azim MK, Taha M, Salar U, Khan KM, et al.
    Bioorg Chem, 2017 06;72:89-101.
    PMID: 28390994 DOI: 10.1016/j.bioorg.2017.03.014
    Discovery and development of carbonic anhydrase inhibitors is crucial for their clinical use as antiepileptic, diurectic and antiglaucoma agents. Keeping this in mind, we have synthesized carbohydrazones 1-27 and evaluated them for their in vitro carbonic anhydrase inhibitory potential. Out of twenty-seven compounds, compounds 1 (IC50=1.33±0.01µM), 2 (IC50=1.85±0.24µM), 3 (IC50=1.37±0.06µM), and 9 (IC50=1.46±0.12µM) have showed carbonic anhydrase inhibition better than the standard drug zonisamide (IC50=1.86±0.03µM). Moreover, compounds 4 (IC50=2.32±0.04µM), 5 (IC50=3.96±0.35µM), 7 (IC50=2.33±0.02µM), and 8 (IC50=2.67±0.01µM) showed good inhibitory activity. Cheminformatic analysis has shown that compounds 1 and 2 possess lead-like properties. In addition, kinetic and molecular docking studies were also performed to investigate the binding interaction between carbohydrazones and carbonic anhydrase enzyme. This study has identified a novel and potent class of carbonic anhydrase inhibitors with the potential to be investigated further.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry
  4. Pustenko A, Nocentini A, Balašova A, Alafeefy A, Krasavin M, Žalubovskis R, et al.
    J Enzyme Inhib Med Chem, 2020 Dec;35(1):245-254.
    PMID: 31790605 DOI: 10.1080/14756366.2019.1695795
    A new series of homosulfocoumarins (3H-1,2-benzoxathiepine 2,2-dioxides) possessing various substitution patterns and moieties in the 7, 8 or 9 position of the heterocylic ring were prepared by original procedures and investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the human (h) hCA I, II, IX and XII. The 8-substituted homosulfocoumarins were the most effective hCA IX/XII inhibitors followed by the 7-substituted derivatives, whereas the substitution pattern in position 9 led to less effective binders for the transmembrane, tumour-associated isoforms IX/XII. The cytosolic isoforms hCA I and II were not inhibited by these compounds, similar to the sulfocoumarins/coumarins investigated earlier. As hCA IX and XII are validated anti-tumour targets, with one sulphonamide (SLC-0111) in Phase Ib/II clinical trials, finding derivatives with better selectivity for inhibiting the tumour-associated isoforms over the cytosolic ones, as the homosulfocoumarins reported here, is of crucial importance.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry
  5. Bozdag M, Alafeefy AM, Vullo D, Carta F, Dedeoglu N, Al-Tamimi AM, et al.
    Bioorg Med Chem, 2015 Dec 15;23(24):7751-64.
    PMID: 26639945 DOI: 10.1016/j.bmc.2015.11.023
    Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6-322nM against hCA I, of 0.06-85.4nM against hCA II; of 6.7-152nM against hCA IX and of 0.49-237nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry*
  6. Imran S, Taha M, Ismail NH, Fayyaz S, Khan KM, Choudhary MI
    Bioorg Chem, 2015 Oct;62:83-93.
    PMID: 26275866 DOI: 10.1016/j.bioorg.2015.08.001
    This article describes discovery of 29 novel bisindolylmethanes consisting of thiourea moiety, which had been synthesized through three steps. These novel bisindolylmethane derivatives evaluated for their potential inhibitory activity against carbonic anhydrase (CA) II. The results for in vitro assay of carbonic anhydrase II inhibition activity showed that some of the compounds are capable of suppressing the activity of carbonic anhydrase II. Bisindoles having halogen at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. Derivatives showing inhibition activity docked to further, understand the binding behavior of these compounds with carbonic anhydrase II. Docking studies for the active compound 3j showed that nitro substituent at para position fits into the core of the active site. The nitro substituent of compound 3j is capable of interacting with Zn ion. This interaction believed to be the main factor causing inhibition activity to take place.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis*; Carbonic Anhydrase Inhibitors/pharmacology*
  7. Khor PY, Mohd Aluwi MFF, Rullah K, Lam KW
    Eur J Med Chem, 2019 Dec 01;183:111704.
    PMID: 31557608 DOI: 10.1016/j.ejmech.2019.111704
    Curcumin is a small organic molecule with pleiotropic biological activities. However, its multiple structural-pharmacokinetic challenges prevent its development into a clinical drug. Various structural modifications have been made to improve its drug profile. In this review, we focus on the methods adopted in the synthesis of asymmetric curcumin derivatives and their biological activities and forecast the future of this exciting class of compounds in the field of medicine.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry
  8. Bozdag M, Alafeefy AM, Altamimi AM, Carta F, Supuran CT, Vullo D
    Bioorg Med Chem, 2017 05 15;25(10):2782-2788.
    PMID: 28389112 DOI: 10.1016/j.bmc.2017.03.054
    We report a series of novel metanilamide-based derivatives 3a-q bearing the 2-mercapto-4-oxo-4H-quinazolin-3-yl moiety as tail. All compounds were synthesized by means of straightforward condensation procedures and were investigated in vitro for their inhibition potency against the human (h) carbonic anhydrase (CA; EC 4.2.1.1.1) isoforms I, II, IX and XII. Among all compounds tested the 6-iodo 3g and the 7-fluoro 3i derivatives were the most potent inhibitors against the tumor associated CA IX and XII isoform (KIs 1.5 and 2.7nM respectively for the hCA IX and KIs 0.57 and 1.9nM respectively for the hCA XII). The kinetic data reported here strongly support compounds of this type for their future development as radiotracers in tumor pathologies which are strictly dependent on the enzymatic activity of the hCA IX and XII isoforms.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis*; Carbonic Anhydrase Inhibitors/metabolism; Carbonic Anhydrase Inhibitors/chemistry
  9. Bozdag M, Alafeefy AM, Altamimi AM, Vullo D, Carta F, Supuran CT
    Bioorg Med Chem, 2017 01 15;25(2):677-683.
    PMID: 27939347 DOI: 10.1016/j.bmc.2016.11.039
    Herein we report for the first time a series of 2-benzamido-N-(2-oxo-4-(methyl/trifluoromethyl)-2H-chromen-7-yl) benzamide 3a-f and substituted quinazolin-4(3H)-ones and 2H-benzo[e][1,2,4]thiadiazin-3(4H)-one 1,1-dioxides (5, 6, 8 and 10a-c) as selective inhibitors of the tumor associated hCA IX and XII isoforms. Among the compounds reported the trifluoromethyl derivative 3d resulted the most potent against these CA isoforms with KIs of 10.9 and 6.7nM.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology*; Carbonic Anhydrase Inhibitors/chemistry
  10. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019;20(10):1041-1057.
    PMID: 30767741 DOI: 10.2174/1389450120666190214121342
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

    Matched MeSH terms: Carbonic Anhydrase Inhibitors/therapeutic use
  11. Tamilvanan S, Kumar BA
    Drug Dev Ind Pharm, 2011 Sep;37(9):1003-15.
    PMID: 21417616 DOI: 10.3109/03639045.2011.555407
    Acetazolamide (ACZM)-loaded anionic, cationic, and neutral-charged oil-in-water nanosized emulsions were prepared and compared with their mean droplet diameter, surface charge, entrapment efficiency, freeze-thaw cycling stability, in vitro drug release, and transcorneal permeation.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemistry*
  12. Hashmi S, Khan S, Shafiq Z, Taslimi P, Ishaq M, Sadeghian N, et al.
    Bioorg Chem, 2021 02;107:104554.
    PMID: 33383322 DOI: 10.1016/j.bioorg.2020.104554
    With the fading of 'one drug-one target' approach, Multi-Target-Directed Ligands (MTDL) has become a central idea in modern Medicinal Chemistry. The present study aimed to design, develop and characterize a novel series of 4-(Diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) and evaluates their biological activity against cholinesterase, carbonic anhydrases and α-glycosidase enzymes. The hCA I isoform was inhibited by these novel 4-(diethylamino)-salicylaldehyde-based thiosemicarbazones (3a-p) in low nanomolar levels, the Ki of which differed between 407.73 ± 43.71 and 1104.11 ± 80.66 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 323.04 ± 56.88 to 991.62 ± 77.26 nM. Also, these novel 4-(diethylamino)-salicylaldehyde based thiosemicarbazones (3a-p) effectively inhibited AChE, with Ki values in the range of 121.74 ± 23.52 to 548.63 ± 73.74 nM. For BChE, Ki values were obtained with in the range of 132.85 ± 12.53 to 618.53 ± 74.23 nM. For α-glycosidase, the most effective Ki values of 3b, 3k, and 3g were with Ki values of 77.85 ± 10.64, 96.15 ± 9.64, and 124.95 ± 11.44 nM, respectively. We have identified inhibition mechanism of 3b, 3g, 3k, and 3n on α-glycosidase AChE, hCA I, hCA II, and BChE enzyme activities. Hydrazine-1-carbothioamide and hydroxybenzylidene moieties of compounds play an important role in the inhibition of AChE, hCA I, and hCA II enzymes. Hydroxybenzylidene moieties are critical for inhibition of both BChE and α-glycosidase enzymes. The findings of in vitro and in silico evaluations indicate 4-(diethylamino)-salicylaldehyde-based thiosemicarbazone scaffold to be a promising hit for drug development for multifactorial diseases like Alzheimer's disease.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/metabolism; Carbonic Anhydrase Inhibitors/chemistry
  13. Ishaq M, Taslimi P, Shafiq Z, Khan S, Ekhteiari Salmas R, Zangeneh MM, et al.
    Bioorg Chem, 2020 07;100:103924.
    PMID: 32442818 DOI: 10.1016/j.bioorg.2020.103924
    In recent decade, the entrance of α-N-heterocyclic thiosemicarbazones derivates (Triapne, COTI-2 and DpC) in clinical trials for cancer and HIV-1 has vastly increased the interests of medicinal chemists towards this class of organic compounds. In the given study, a series of eighteen new (3a-r) 3-ethoxy salicylaldehyde-based thiosemicarbazones (TSC), bearing aryl and cycloalkyl substituents, were synthesized and assayed for their pharmacological potential against carbonic anhydrases (hCA I and hCA II), cholinesterases (AChE and BChE) and α-glycosidase. The hCA I isoform was inhibited by these novel 3-ethoxysalicylaldehyde thiosemicarbazone derivatives (3a-r) in low nanomolar levels, the Ki of which differed between 144.18 ± 26.74 and 454.92 ± 48.32 nM. Against the physiologically dominant isoform hCA II, the novel compounds demonstrated Kis varying from 110.54 ± 14.05 to 444.12 ± 36.08 nM. Also, these novel derivatives (3a-r) effectively inhibited AChE, with Ki values in the range of 385.38 ± 45.03 to 983.04 ± 104.64 nM. For BChE was obtained with Ki values in the range of 400.21 ± 35.68 to 1003.02 ± 154.27 nM. For α-glycosidase the most effective Ki values of 3l, 3n, and 3q were with Ki values of 12.85 ± 1.05, 16.03 ± 2.84, and 19.16 ± 2.66 nM, respectively. Moreover, the synthesized TCSs were simulated using force field methods whereas the binding energies of the selected compounds were estimated using MM-GBSA method. The findings indicate the present novel 3-ethoxy salicylaldehyde-based thiosemicarbazones to be excellent hits for pharmaceutical applications.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors/chemical synthesis; Carbonic Anhydrase Inhibitors/pharmacology; Carbonic Anhydrase Inhibitors/chemistry*
  14. Kashiwagi K, Chono E, Koesters S, Yap PS
    BMC Ophthalmol, 2020 Jun 10;20(1):223.
    PMID: 32522181 DOI: 10.1186/s12886-020-01508-8
    BACKGROUND: Poor persistence with glaucoma therapy can lead to disease progression and subsequent blindness. Persistence with second-line glaucoma combination treatment in a Japanese real-world setting and whether it differed from fixed and unfixed combination drugs was investigated.

    METHODS: This was a retrospective, non-interventional, cohort study using data from a Japanese medical claims database. Patients with glaucoma aged ≥20 years with a first drug claim for glaucoma treatment between 01 July 2005 and 30 October 2014 and with data for > 6 months before and after this first prescription were included. The primary endpoint was duration of drug persistence among glaucoma patients with and without the use of fixed combination drugs in the year following initiation of second-line combination treatment.

    RESULTS: Of 1403 patients included in the analysis, 364 (25.94%) received fixed combination drugs and 1039 (74.06%) received unfixed combination drugs as second-line treatment. Baseline characteristics were generally comparable between the groups. A total of 39.01% of patients on fixed combination drugs, compared with 41.67% of patients on unfixed combination drugs, persisted on their glaucoma drugs 12 months post second-index date. Median persistence durations for the fixed combination drugs and unfixed combination drugs groups were 6 (95% confidence interval [CI]: 5-8) and 7 months (95% CI 6-9), respectively. Patients who received prostaglandin analogs (PGAs) were the most persistent with their treatment (n = 99, 12.84%). Patients diagnosed with primary open-angle glaucoma were less likely to experience treatment modification (hazard ratio [HR]: 0.800, 95% CI 0.649-0.986, P = 0.036), while those diagnosed with secondary glaucoma were more likely to experience treatment modification (HR: 1.678, 95% CI 1.231-2.288, P = 0.001) compared with glaucoma suspects.

    CONCLUSIONS: In this retrospective claims database study, the persistence rate of second-line glaucoma combination treatment was low, with no difference in persistence between glaucoma patients receiving unfixed combination drugs compared with fixed combination drugs. Patients on PGA showed greater persistence rates compared with other treatments.

    Matched MeSH terms: Carbonic Anhydrase Inhibitors/therapeutic use
  15. Amy Suzana Abu Bakar, Norhafiza Razali, Mohammad Daniel Shafiq Hassan, Renu Agarwal
    MyJurnal
    Glaucoma is an optic neuropathy characterised by optic nerve degeneration associated with
    visual field defects. It remains the world’s number one cause of irreversible blindness and
    patients usually present at late stage of the disease since it is generally asymptomatic until
    severe. The disease is subdivided into primary and secondary with primary open-angle
    glaucoma (POAG) being the most common type. At present, lowering the intraocular pressure
    (IOP) remains the only proven efficient approach in delaying the onset or preventing the
    progression of the disease. Medical treatment with topical antiglaucoma agents is the
    treatment of choice in open angle glaucoma. The use of antiglaucoma drugs aims to reduce
    IOP by enhancing aqueous humour (AH) outflow, reducing AH production, or both. The choice
    to use any available treatment option should be carefully considered in an attempt to maximise
    benefits and reducing the risk of developing adverse drug reactions. This review highlights the
    six classes of ocular hypotensive agents currently in use for POAG treatment including
    prostaglandin analogues; -adrenergic receptor blockers; -2 adrenergic receptor stimulants;
    carbonic anhydrase inhibitors; muscarinic receptor stimulants; rho kinase inhibitors with
    regards to their mechanism/s of action and potential adverse drug reactions, and
    antiglaucoma fixed drug combinations.
    Matched MeSH terms: Carbonic Anhydrase Inhibitors
  16. Zhang L, Hussain Z, Ren Z
    Curr Drug Targets, 2019 Feb 14.
    PMID: 30767742 DOI: 10.2174/1389450120666190214141626
    BACKGROUND: Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess cerebrospinal fluid (CSF) is accumulated in the brain's ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, blurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.

    OBJECTIVE: The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of effectiveness of employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for treatment of hydrocephalus has also been appraised.

    RESULTS: Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for management of NPH and prevention of secondary sensory/intellectual complications.

    CONCLUSION: Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of cerebrospinal fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.

    Matched MeSH terms: Carbonic Anhydrase Inhibitors
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