Human Carbonic Anhydrase Isoforms Research Articles

1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Novel 1,2,4-triazole-maleamic acid derivatives: synthesis and evaluation as anticancer agents with carbonic anhydrase inhibitory activity

Hybrid compounds with 1,2,4-triazole ring and a hydrazone moiety were designed and synthesized by amine acylation of uncommon triaminogunidine derivatives using maleic anhydride. Synthesized compounds were characterized by various spectral techniques, including FTIR, 1H NMR, 13C NMR, and HRMS. Furthermore, the proposed structure of TM-2 was resolved by single-crystal X-ray analysis. The compounds were evaluated for their anticancer activity in vitro against the colon cancer cell line HCT116 and the ovarian cancer cell line A2780. Among them, some compounds, TM-3, TM-4, and TM-14, exhibited remarkable antiproliferative activity in the cell line A2780, with IC50 values of 6.11, 5.15, and 5.93 µM, respectively. Further investigation revealed that these compounds could inhibit cancerous cell growth by inducing an increase in caspase-3 activity. In addition, antioxidant capabilities, interaction with plasmid pBR322 DNA, and inhibitory effects against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms, namely hCA I and hCA II, of the synthesized compounds were also assessed. Finally, computational studies, such as DFT calculation, molecular docking, and in silico predictions of ADME/T analysis, were conducted to gain an understanding of the specific reactive sites of the compounds, the binding modes in the active sites, and the pharmacokinetic parameters of the newly synthesized hybrid compounds, which were calculated to establish their drug-likeness properties.

In-vitro and in-silico investigations of SLC-0111 hydrazinyl analogs as human carbonic anhydrase I, II, IX, and XII inhibitors.

Two novel series of hydrazinyl-based benzenesulfonamides 9a-j and 10a-j were designed and synthesized using SLC-0111 as the lead molecule. The newly synthesized compounds were evaluated for their inhibitory activity against four different human carbonic anhydrase (hCA) isoforms I, II, IX, and XII. Both the series reported here were practically inactive against the off-target isozyme hCA I. Notably, derivative 10a exhibited superior potency (Ki of 10.2 nM) than acetazolamide (AAZ) against the cytosolic isoform hCA II. The hCA IX and XII isoforms implicated in tumor progression were effectively inhibited with Kis in the low nanomolar range of 20.5-176.6 nM and 6.0-127.5 nM, respectively. Compound 9g emerged as the most potent and selective hCA IX and XII inhibitor with Ki of 20.5 nM and SI of 200.1, and Ki of 6.0 nM and SI of 683.7, respectively, over hCA I. Furthermore, six compounds (9a, 9h, 10a, 10g, 10i, and 10j) exhibited significant inhibition toward hCA IX (Kis = 27.0, 41.1, 27.4, 25.9, 40.7, and 30.8 nM) relative to AAZ and SLC-0111 (Kis = 25.0 and 45.0 nM, respectively). These findings underscore the potential of these derivatives as potent and selective inhibitors of hCA IX and XII over the off-target hCA I and II.

Exploring Novel Schiff Base Compounds Derived from Benzothiophene-3- carboxaldehyde Hydrazones: In vitro and In silico Evaluation as Potential Inhibitors of Cholinesterases and Carbonic Anhydrases I-II

In this study, inhibitions of some cytosolic enzymes were evaluated. Inhibitors of these enzymes can help illuminate and treat many related diseases (Alzhaimer, Parkinson's, Glaucoma, etc.). It is aimed to minimize drug side effects with multiple effects in one molecule. For this purpose in vitro effects of two benzothiophene Schiff bases on cholinesterases (AChE and BuChE) and human carbonic anhydrase isoforms (CAI and CAII) were investigated. Molecular modeling studies were carried out to elucidate the inhibition mechanism of two effective compounds on these enzymes. Then, two benzothiophene Schiff bases (1a and 1b compounds) were tested in vitro on these enzymes. The in vitro study results supported the in silico study results. Obtained results revealed that the benzothiophene derivatives inhibited the enzymes significantly. Ki values for CAI isoenzyme were determined to be in the range of 58.82 ± 7.96-126.28 ± 26.22 nM; for the CAII isoenzyme in the range of 27.86 ± 3.76-74.30 ± 7.89 nM; for acetylcholinesterase in the range of 1.31 ± 0.39-2.16 ± 1.01 nM; for butyrylcholinesterase in the range of 1.80 ± 0.27-2.01 ± 1.67 nM. Compared to the AZA control compound, 1b has demonstrated more strong inhibitory effect against CAI and CAII. Wherease compared with other control compound Tacrine, both compounds showed more potent inhibitory effect for cholinesterases (AChE and BuChE).

Exploring rhodanine linked enamine-carbohydrazide derivatives as mycobacterial carbonic anhydrase inhibitors: Design, synthesis, biological evaluation, and molecular docking studies.

With the rise of multidrug-resistant tuberculosis, the imperative for an alternative and superior treatment regimen, incorporating novel mechanisms of action, has become crucial. In pursuit of this goal, we have developed and synthesized a new series of rhodanine-linked enamine-carbohydrazide derivatives, exploring their potential as inhibitors of mycobacterial carbonic anhydrase. The findings reveal their efficacy, displaying notable selectivity toward the mycobacterial carbonic anhydrase 2 (mtCA 2) enzyme. While exhibiting moderate activity against human carbonic anhydrase isoforms, this series demonstrates promising selectivity, positioning these compounds as potential antitubercular agents. Compound 6d was the best one from the series with a Ki value of 9.5 µM toward mtCA 2. Most of the compounds displayed moderate to good inhibition against the Mtb H37Rv strain; compound 11k showed a minimum inhibitory concentration of 1 µg/mL. Molecular docking studies revealed that compounds 6d and 11k show metal coordination with the zinc ion, like classical CA inhibitors.

Design, synthesis, and biological evaluation of 3-benzenesulfonamide-linked 3-hydrazinoisatin derivatives as carbonic anhydrase inhibitors.

A new series of isatin-linked benzenesulfonamide derivatives (9a-w) were synthesized using the tail approach and assayed for their inhibitory potency against four different human carbonic anhydrase (hCA) isoforms, hCA I, II, IX, and XII. Most of these synthesized compounds exhibited interesting inhibition potency against isoforms hCA I, IX, and XII in the nanomolar range and by taking the standard drug acetazolamide. The most potent compounds in the case of hCA I were 9c (435.8 nM) and 9s (956.4 nM), for hCA IX, 9a (60.5 nM), 9d (95.6 nM), 9g (92.1 nM), and 9k (75.4 nM), and for hCA XII, 9p (84.5 nM). However, these compounds showed more selectivity toward hCA IX over hCA I, II, and XII. Thus, these compounds can be further developed as potential lead molecules for the development of isoform-selective hCA IX inhibitors with further structural modifications.

Synthetic Approaches to Novel Human Carbonic Anhydrase Isoform Inhibitors Based on Pyrrol-2-one Moiety.

New dihydro-pyrrol-2-one compounds, featuring dual sulfonamide groups, were synthesized through a one-pot, three-component approach utilizing trifluoroacetic acid as a catalyst. Computational analysis using density functional theory (DFT) and condensed Fukui function explored the structure-reactivity relationship. Evaluation against human carbonic anhydrase isoforms (hCA I, II, IX, XII) revealed potent inhibition. The widely expressed cytosolic hCA I was inhibited across a range of concentrations (KI 3.9-870.9 nM). hCA II, also cytosolic, exhibited good inhibition as well. Notably, all compounds effectively inhibited tumor-associated hCA IX (KI 1.9-211.2 nM) and hCA XII (low nanomolar). Biological assessments on MCF7 cancer cells highlighted the compounds' ability, in conjunction with doxorubicin, to significantly impact tumor cell viability. These findings underscore the potential therapeutic relevance of the synthesized compounds in cancer treatment.

Role of human carbonic anhydrase isoforms VA and VB in obesity: Implications, mechanisms, and therapeutic prospects

Role of human carbonic anhydrase isoforms VA and VB in obesity: Implications, mechanisms, and therapeutic prospects

1,2,3-Triazole-based esters and carboxylic acids as nonclassical carbonic anhydrase inhibitors capable of cathepsin B inhibition.

Herein, we report the design and synthesis of a library of 28 new 1,2,3-triazole derivatives bearing carboxylic acid and ester moieties as dual inhibitors of carbonic anhydrase (CA) and cathepsin B enzymes. The synthesised compounds were assayed in vitro for their inhibition potential against four human CA (hCA) isoforms, I, II, IX and XII. The carboxylic acid derivatives displayed low micromolar inhibition against hCA II, IX and XII in contrast to the ester derivatives. Most of the target compounds showed poor inhibition against the hCA I isoform. 4-Fluorophenyl appended carboxylic acid derivative 6c was found to be the most potent inhibitor of hCA IX and hCA XII with a KI value of 0.7 μM for both the isoforms. The newly synthesised compounds showed dual inhibition towards CA as well as cathepsin B. The ester derivatives exhibited higher % inhibition at 10-7 M concentration as compared with the corresponding carboxylic acid derivatives against cathepsin B. The results from in silico studies of the target compounds with the active site of cathepsin B were found in good correlation with the in vitro results. Moreover, two compounds, 5i and 6c, showed cytotoxic activity against A549 lung cancer cells, with IC50 values lower than 100 μM.

Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors.

The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a-3p) in good to excellent yields (78%-91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic studies. Single crystal X-ray studies for 3a, 3d, and 3i verified the proposed structure. The newly developed sulfonamide-phosphonates were evaluated for their inhibitory properties against four isoforms of human carbonic anhydrase (hCA I, II, IX, and XII). The results demonstrated that they exhibited greater potency in inhibiting hCA XII compared to hCA I, II, and IX, with Ki ranging from 5.1 to 51.1 nM. Compounds 3l and 3p displayed the highest potency, exhibiting selectivity ratios of I/XII >298.7 and 8.5, and II/XII ratios of 678.1 and 142.1, respectively. Molecular docking studies were conducted to explore their binding patterns within the binding pocket of CA XII. The results revealed that the sulfonamide NH group coordinated with the Zn2+ ion, and hydrogen bond interactions were observed with residue Thr200. Additionally, hydrophobic interactions were identified between the benzenesulfonamide phenyl ring and Leu198. Compounds 3p and 3l exhibited an additional hydrogen bonding interaction with other amino acid residues. These supplementary interactions may contribute to the enhanced potency and selectivity of these compounds toward the CA XII isoform.

Prospects for the application of inhibitors of carbonic anhydrase isoforms IX and XII in oncology

Human carbonic anhydrase isoforms IX and XII play a key role in maintaining acid-base balance in solid tumors, creating a favorable microenvironment for the growth, invasion and metastasis of tumor cells. In the last few years, a number of scientific groups have published results that inhibition of isoforms IX and XII significantly increases the effectiveness of classical chemotherapy, makes it possible to suppress the resistance of tumor cells to chemotherapy and increase their sensitivity to the used drugs (including reducing the dose of cytostatics). In the review, we analyzed the scientific literature on the role of carbonic anhydrase isoforms IX and XII in carcinogenesis and on the combined effect of carbonic anhydrase inhibitors with antitumor drugs.

Identification of 3-(5-cyano-6-oxo-pyridin-2-yl)benzenesulfonamides as novel anticancer agents endowed with EGFR inhibitory activity.

New 5-cyano-6-oxo-pyridine-based sulfonamides (6a-m and 8a-d) were designed and synthesized to potentially inhibit both the epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), with anticancer properties. First, the in vitro anticancer activity of each target substance was tested using Henrietta Lacks cancer cell line and M.D. anderson metastasis breast cancer cell line cells. Then, the possible CA inhibition against the human CA isoforms I, II, and IX was investigated, together with the EGFR inhibitory activity, with the most powerful derivatives. The neighboring methoxy group may have had a steric effect on the target sulfonamides, which prevented them from effectively inhibiting the CA isoforms while effectively inhibiting the EGFR. The effects of the 5-cyanopyridine derivatives 6e and 6l on cell-cycle disruption and the apoptotic potential were then investigated. To investigate the binding mechanism and stability of the target molecules, thorough molecular modeling assessments, including docking and dynamic simulation, were performed.

Molecular hybrids integrated with imidazole and hydrazone structural motifs: Design, synthesis, biological evaluation, and molecular docking studies

In the present work, a series of compounds containing imidazole and hydrazone structural frameworks were synthesized and characterized using various spectral techniques, including 1H NMR, 13C NMR, FTIR, and HRMS. Synthesized compounds were subjected to screening as antiproliferative agents as well as against two physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I and hCA II. Among them, some compounds exhibited remarkable antiproliferative activity with less cytotoxicity activity to healthy cells and significant CA inhibitory activities in contrast to a standard inhibitor with Ki values in the range of 0.49 ± 1.010–739.12 ± 111.35 nM for hCA I (Ki value for standard inhibitor = 271.15 ± 74.620 nM), 64.53 ± 19.44–314.37 ± 54.78 nM for hCA II (Ki value for standard inhibitor = 113.07 ± 20.980 nM). In addition, DFT calculations were performed to get insight into the distinctive reactive sites of all compounds, and subsequently, the reactive centers of the compounds were determined. Moreover, molecular docking studies of the most potent compounds were conducted, and results showed reasonable binding modes in the active sites of hCA I protein (PDB ID: 2CAB), hCA II protein (PDB ID: 3DC3), as well as colon cancer protein (PDB ID: 4UYA and 3DTC). Finally, in silico predictions of ADME and pharmacokinetic parameters indicated that these compounds should have good oral bioavailability.

Keto-bridged dual triazole-linked benzenesulfonamides as potent carbonic anhydrase and cathepsin B inhibitors.

Background: Inhibition of human carbonic anhydrase (hCA) isoforms IX and XII with concurrent inhibition of cathepsin B is a promising approach for targeting cancers. Methods/results: 28 keto-bridged dual triazole-containing benzenesulfonamides were synthesized and tested, following the multitarget approach, for their efficacy as inhibitors of cathepsin B and hCA isoforms (I, II, IX, XII). The synthesized compounds showed excellent inhibition of CA isoforms (IX and XII)and cathepsin B. Compound 8i exhibited better and more selective inhibition of the cancer-associated isoform hCA IX as compared with acetazolamide (reference drug) and SLC-0111 (potent lead ascarbonic anhydraseinhibitor). Molecular docking studies were also carried out. Conclusion: The present work gives important generalizations for the development of isoform-selective hCA inhibitors endowed with anti-cathepsin properties.

Enzyme inhibitory potential of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II enzymes: an in vitro and molecular docking study

In this study, the in vitro effects of some indole Schiff bases on acetylcholinesterase and human carbonic anhydrase isoforms I and II were investigated. A series of N-methylindole hydrazide/hydrazone derivatives (1a-1t) were tested on these enzymes. The interactions of the synthesized indole derivatives with target enzymes were studied by molecular docking methodology. The results revealed that indole derivative Schiff base compounds inhibited the enzymes significantly. Ki values for hCAI isoenzyme were determined to be in the range of 36.18 ± 3.07–224.29 ± 5.78 nM; for the hCAII isoenzyme in the range of 31.30 ± 2.63–201.64 ± 7.25 nM; for acetylcholinesterase in the range of 6.82 ± 0.72–110.30 ± 9.26 nM. Compared to the control compound Acetazolamide (AZA), 1k and 1p were found to have the best inhibitory effect for hCAI; 1p was found to be the best inhibitory effect for hCAII. Compared to the control compound Tacrine (TAC), 1s showed the best inhibitory effect for AChE. In vitro results were verified with the results obtained by docking studies and interactions with enzymes were demonstrated. Communicated by Ramaswamy H. Sarma

Screening Campaign and Docking Investigations in Identifying New Hit Compounds as Inhibitors of Human Carbonic Anhydrases Expressed In Tumour Cells.

The tumor-expressed human carbonic anhydrase (hCA) isoforms hCA IX and hCA XII have been extensively studied to develop anticancer agents targeting solid tumors in combined therapy. These CA isoforms are considered key factors in controlling tumor microenvironment (TME) of cancer lines that develop high metastatic activity. Herein, we report the discovery of potent hCA IX/hCA XII inhibitors that were disclosed through a screening campaign on an in-house collection of arylsulfonamides preliminary tested toward other hCAs. Among them, the N-(4-sulfamoylphenyl)naphthalene-2-carboxamide (12) and N-(4-sulfamoylphenyl)-3,4-dihydroisoquinoline-2(1H)-carbothioamide (15) proved to be the most intriguing hCA IX/hCA XII inhibitors displaying favourable selectivity ratios over widespread hCA I and hCA II isoforms. To explore their binding mode, we conducted docking studies that described the poses of the best inhibitors in the catalytic site of hCA IX and hCA XII, thus suggesting the privileged pattern of interactions. These structural findings might further improve the knowledge for a successful identification of new sulfonamides as adjuvant agents in cancer management.

Exploring novel anticancer pyrazole benzenesulfonamides featuring tail approach strategy as carbonic anhydrase inhibitors

This study aimed to design potent carbonic anhydrase inhibitors (CAIs) based on pyrazole benzenesulfonamide core. Nine series of substituted pyrazole benzenesulfonamide compounds were synthesized with variable groups like sulphamoyl group as in compounds 4a-e, its bioisosteric carboxylic acid as in compounds 5a-e and 8e, ethyl carboxylate ester as in compounds 6a-e and 9a-e, which were designed as potential prodrugs, isothiazole ring as in compound 7, hydrazide derivative 10e, hydroxamic acid derivatives 11a-e and semicarbazide derivatives 12a-c,e. All the synthesized compounds were investigated for their carbonic anhydrase (CA) inhibitory activity against two human CA isoforms hCA IX and hCA XII and compared to acetazolamide (AAZ). Also, the compounds were assessed for their anticancer activity against 60 cancer cell lines according to the US NCI protocol. Compounds 4b, 5b, 5d, 5e, 6b, 9b, 9e and 11b revealed significant inhibitory activity against both isoforms hCA IX and hCA XII, while 6e, 9d, 11d and 11e showed significant inhibitory activity against hCA XII only compared to acetazolamide as a reference. This would highlight these compounds as promising anticancer drugs. Moreover, compound 6e revealed a remarkable cytostatic activity against CNS cancer cell line (SF-539; TGI = 5.58 μM), renal cancer cell line (786–0; TGI = 4.32 μM) and breast cancer cell line (HS 578 T; TGI = 5.43 μM). Accordingly, compound 6e was subjected to cell cycle analysis and apoptotic assay on the abovementioned cell lines at the specified GI50 (0.45, 0.89 and 1.18 μM, respectively). Also, it revealed the increment of total apoptotic cells percentage in 786–0 (53.19%), SF-539 (46.11%) and HS 578 T (43.55%) relative to the control cells (2.07, 2.64 and 2.52%, respectively). In silico prediction of BBB permeability showed that most of the calculations for compound 6e resulted as BBB (+), which is required for a compound targeting CNS. Further, the interaction of the most active compounds with the key amino acids in the active sites of hCA IX and hCA XII was highlighted by molecular docking analysis.

Potent inhibitors of tumor associated carbonic anhydrases endowed with cathepsin B inhibition.

Twenty-one novel extended analogs of acetazolamide were synthesized and screened in vitro for their inhibition efficacy against human carbonic anhydrase (hCA) isoforms I, II, IX, XII, and cathepsin B. The majority of the compounds were found to be effective inhibitors of tumor-associated hCA IX and XII, and poor inhibitors of cytosolic hCA I. Despite the strong to moderate inhibition potential possessed by these compounds toward another cytosolic isoform hCA II, some of them demonstrated better potency against hCA IX and/or XII isoforms as compared to hCA II. Four compounds (11f, 11g, 12c, and 12g) effectively inhibited hCA IX and/or XII isoforms with considerable selectivity over the off-targets hCA I and II. Interestingly, five compounds,including 11f, 11g, 12c, 12d, and 12g, inhibited hCA IX even better than the clinically used acetazolamide. Some of the novel synthesized compounds exhibited higher anti-cathepsin B potential than acetazolamide, with % inhibition of around 50%, at a concentration of 10-7 M. Further, two compounds (12g and 12c) that showed effective and selective inhibition activity profiles against hCA IX and XII were additionally found to be effective inhibitors of cathepsin B.

Design and synthesis of sulfonamides incorporating a biotin moiety: Carbonic anhydrase inhibitory effects, antiproliferative activity and molecular modeling studies

Sulfonamides constitute an important class of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. Herein we have accomplished the conjugation of biotin with an ample number of sulfonamide motifs with the aim of testing them in vitro as inhibitors of the human carbonic anhydrase (hCA) isoforms I and II (cytosolic isozymes), as well as hCA IX and XII (transmembrane, tumor-associated enzymes). Most of these newly synthesized compounds exhibited interesting inhibition profiles, with activities in the nanomolar range. The presence of a 4-F-C6H4 moiety, also found in SLC-0111, afforded an excellent selectivity towards the tumor-associated hypoxia-induced hCA isoform XII with an inhibition constant (KI) of 4.5 nM. The 2-naphthyl derivative was the most potent inhibitor against hCA IX (KI = 6.2 nM), 4-fold stronger than AAZ (KI = 25 nM) with very good selectivity. Some compounds were chosen for antiproliferative activity testing against a panel of 3 human tumor cell lines, one compound showing anti-proliferative activity on glioblastoma, triple-negative breast cancer, and pancreatic carcinoma cell lines.

İMİDAZOLİNON BAZLI SÜLFONAMİD TÜREVLERİ: SENTEZ, KARAKTERİZASYON VE BAZI METABOLİK ENZİMLERE KARŞI İNHİBİTÖR ÖZELLİKLERİ

Objective: The purpose of the work was to investigate new synthetic compounds of imidazolinone-based sulfonamide derivatives as potent and selective enyzme inhibitors. A number of compounds synthesized and their inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II were investigated. Material and Method: The identity of the compounds has been confirmed by HRMS, 1H NMR, and 13C NMR. The pharmacological potential of the compounds has been determined by in vitro enzyme-based assays. Result and Discussion: In this study, a series of imidazolinone-based sulfonamide derivatives were synthesized from 4-(2,4-dimethoxybenzylidene)-2-phenyloxazol-5(4H)-one, sodium acetate, glacial acetic acid, and suitable sulfonamide derivatives such as sulfaguanidine (3), sulfanilamide (4), sulfadiazine (5). These compounds showed potent inhibitory action against acetylcholine esterase (AChE), and human (h) carbonic anhydrase (CA) isoforms I and II. Compound 4 (Ki=19.53±1.23 nM) was a potent and selective inhibitor against hCA I while compound 3 (Ki=16.49±2.20 nM) was found to be potent inhibitor against hCA II. Compound 5 with Ki of 11.68±1.45 nM showed a potent inhibitory effect against the AChE enzyme. Imidazolinone-based sulfonamides can be used in the design of selective CAs inhibitors and anti-Alzheimer's compounds for further studies.