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1.
In this work, the inhibitory effect of some symmetric sulfamides derived from phenethylamines were determined against human carbonic anhydrase (hCA) I, and II isoenzymes, and compared with standard compound acetazolamide. IC50 values were obtained from the Enzyme activity (%)-[Symmetric sulfamides] graphs. Also, Ki values were calculated from the Lineweaver-Burk graphs. Some symmetric sulfamides compounds ( 11 – 18 ) demonstrated excellent inhibition effects against hCA I, and II isoenzymes. These compounds demonstrated effective inhibitory profiles with IC50 values in ranging from 21.66–28.88 nM against hCA I, 14.44–30.13 nM against hCA II. Among these compounds, the best Ki value for hCA I (Ki: 8.34±1.60 nM) and hCA II (Ki: 16.40±1.00 nM) is compound number 11 . Besides, the IC50 value of acetazolamide used as a standard was determined as hCA I, hCA II 57.75 nM, 49.50 nM, respectively. Moreover, in silico ADME-Tox study showed that all synthesized compounds ( 11 – 18 ) had good oral bioavailability in light of Jorgensen's rule of three, and of Lipinski's rule of five. 相似文献
2.
Uur Tutar Ümit M. Koyiit Hayreddin Gezegen 《Journal of biochemical and molecular toxicology》2019,33(4)
A series of 1,3‐bis‐chalcone derivatives ( 3a‐i, 6a‐i and 8 ) were synthesized and evaluated antimicrobial, antibiofilm and carbonic anhydrase inhibition activities. In this evaluation, 6f was found to be the most active compound showing the same effect as the positive control against Bacillus subtilis and Streptococcus pyogenes in terms of antimicrobial activity. Biofilm structures formed by microorganisms were damaged by compounds at the minimum inhibitory concentration value between 0.5% and 97%.1,3‐bis‐chalcones ( 3a‐i, 6a‐i and 8 ) showed good inhibitory action against human (h) carbonic anhydrase (CA) isoforms I and II. hCA I and II were effectively inhibited by these compounds, with K i values in the range of 94.33 ± 13.26 to 787.38 ± 82.64 nM for hCA I, and of 100.37 ± 11.41 to 801.76 ± 91.11 nM for hCA II, respectively. In contrast, acetazolamide clinically used as CA inhibitor showed K i value of 1054.38 ± 207.33 nM against hCA I, and 983.78 ± 251.08 nM against hCA II, respectively. 相似文献
3.
Sinan Bilginer Baris Gonder Halise Inci Gul Ruya Kaya Ilhami Gulcin Baris Anil 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):325-329
Abstract A series of compounds incorporating 3-(3-(2/3/4-substituted phenyl)triaz-1-en-1-yl) benzenesulfonamide moieties were synthesised and their chemical structure was confirmed by physico-chemical methods. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were evaluated against human isoforms hCA I and II. KI values of these sulphonamides were in the range of 21?±?4–72?±?2?nM towards hCA I and in the range of 16?±?6–40?±?2?nM against hCA II. The 4-fluoro substituted derivative might be considered as an interesting lead due to its effective inhibitory action against both hCA I and hCA II (KIs of 21?nM), a profile rarely seen among other sulphonamide CA inhibitors, making it of interest in systems where the activity of the two cytosolic isoforms is dysregulated. 相似文献
4.
Hüseyin Kekeçmuhammed Michael Tapera Ekrem Aydoğdu Emin Sarıpınar Elanur Aydin Karatas Eda Mehtap Uc Mesut Akyuz Burak Tüzün İlhami Gulcin Rıfat Emin Bora İlhan Özer İlhan 《化学与生物多样性》2023,20(6):e202200886
In an attempt to identify potential active anticancer agents with low cytotoxic properties and CA inhibitors, a new series of hybrid compounds incorporating imidazole ring and hydrazone moiety as part of their structure were synthesized by aza-Michael addition reaction followed by intramolecular cyclization. The structure of synthesized compounds was elucidated using various spectral techniques. Synthesized compounds were evaluated for their in vitro anticancer (prostate cell lines; PC3) and CA inhibitory (hCA I and hCA II) activity. Among them, some compound displayed remarkable anticancer activity and CA inhibitory activity with Ki values in range of 17.53±7.19–150.50±68.87 nM against cytosolic hCA I isoform associated with epilepsy, and 28.82±14.26–153.27±55.80 nM against dominant cytosolic hCA II isoforms associated with glaucoma. Furthermore, the theoretical parameters of the bioactive molecules were calculated to establish their drug-likeness qualities. The proteins used for the calculations are prostate cancer protein (PDB ID: 3RUK and 6XXP). ADME/T analysis was carried out to examine the drug properties of the studied molecules. 相似文献
5.
Zeynep Kksal Zuhal Alm Songül Bayrak lhami Gülin Hasan
zdemir 《Journal of biochemical and molecular toxicology》2019,33(5)
Human carbonic anhydrase I and II isoenzymes (hCA I and II) and acetylcholinesterase (AChE) are important metabolic enzymes that are closely associated with various physiological and pathological processes. In this study, we investigated the inhibition effects of some sulfonamides on hCA I, hCA II, and AChE enzymes. Both hCA isoenzymes were purified by Sepharose‐4B‐L‐Tyrosine‐5‐amino‐2‐methylbenzenesulfonamide affinity column chromatography with 1393.44 and 1223.09‐folds, respectively. Also, some inhibition parameters including IC50 and Ki values were determined. Sulfonamide compounds showed IC 50 values of in the range of 55.14 to 562.62 nM against hCA I, 55.99 to 261.96 nM against hCA II, and 98.65 to 283.31 nM against AChE. Ki values were in the range of 23.40 ± 9.10 to 365.35 ± 24.42 nM against hCA I, 45.87 ± 5.04 to 230.08 ± 92.23 nM against hCA II, and 16.00 ± 45.53 to 157.00 ± 4.02 nM against AChE. As a result, sulfonamides had potent inhibition effects on these enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly in the treatment of some disorders. 相似文献
6.
Emine Ö. Karaca Zeynebe Bingöl Nevin Gürbüz İsmail Özdemir İlhami Gülçin 《Journal of biochemical and molecular toxicology》2023,37(2):e23255
A series of vinyl functionalized 5,6-dimethylbenzimidazolium salts are synthesized. All compounds were fully characterized by elemental analyses, MS, 1H-NMR, 13C-NMR, and IR spectroscopy techniques. Enzyme inhibition is a very active area of research in drug design and development. In this study, the synthesized novel benzimidazolium salts were evaluated toward the human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. They demonstrated highly potent inhibition ability against hCA I with Ki values of 484.8 ± 62.6–1389.7 ± 243.2 nM, hCA II with Ki values of 298.9 ± 55.7–926.1 ± 330.0 nM, α-glycosidase with Ki values of 170.3 ± 27–760.1 ± 269 μM, AChE with Ki values of 27.1 ± 3–77.6 ± 1.7 nM, and BChE with Ki values of 21.0 ± 5–61.3 ± 15 nM. As a result, novel vinyl functionalized 5,6-dimethylbenzimidazolium salts (1a–g) exhibited effective inhibition profiles toward studied metabolic enzymes. Therefore, we believe that these results may contribute to the development of new drugs particularly to treat some global disorders including glaucoma, Alzheimer's disease, and diabetes. 相似文献
7.
Leyla Polat Kose Alper Yıldırım Ufuk Atmaca Murat Çelik Saleh H. Alwasel 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1248-1253
The carbonic anhydrases (CAs, EC 4.2.1.1) represent a superfamily of widespread enzymes, which catalyze a crucial biochemical reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Human CA isoenzymes I and II (hCA I and hCA II) are ubiquitous cytosolic isoforms. In this study, a series of hydroperoxides, alcohols, and acetates were tested for the inhibition of the cytosolic hCA I and II isoenzymes. These compounds inhibited both hCA isozymes in the low nanomolar ranges. These compounds were good hCA I inhibitors (Kis in the range of 24.93–97.99?nM) and hCA II inhibitors (Kis in the range of 26.04–68.56?nM) compared to acetazolamide as CA inhibitor (Ki: 34.50?nM for hCA I and Ki: 28.93?nM for hCA II). 相似文献
8.
Halise Inci Gul Parham Taslimi Ilhami Gulcin Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):189-192
4-(3-(4-Substituted-phenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl) benzenesulfonamides (9–16) were successfully synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, and HRMS spectra. Carbonic anhydrase I and II inhibitory effects of the compounds were investigated. Ki values of the compounds were in the range of 316.7?±?9.6–533.1?±?187.8?nM towards hCA I and 412.5?±?115.4–624.6?±?168.2?nM towards hCA II isoenzymes. While Ki values of the reference compound Acetazolamide were 278.8?±?44.3?nM and 293.4?±?46.4?nM towards hCA I and hCA II izoenzymes, respectively. Compound 14 with bromine and compound 13 with fluorine substituents can be considered as the leader compounds of the series because of the lowest Ki values in series to make further detailed carbonic anhydrase inhibiton studies. 相似文献
9.
1H‐indazole molecules reduced the activity of human erythrocytes carbonic anhydrase I and II isoenzymes
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Carbonic anhydrase (CA) is an important metabolic enzyme family closely related to many physiological and pathological processes. Currently, carbonic anhydrase inhibitors are the target molecules in the treatment and diagnosis of many diseases. In present study, we investigated the inhibitory effects of some indazole molecules on the CA‐I and CA‐II isoenzymes isolated from human erythrocytes. We showed that human CA‐I and CA‐II activities were reduced by of some indazoles at low concentrations. IC50 values, Ki constants, and inhibition types for each indazole molecule were determined. The indazoles showed Ki constants in a range of 0.383 ± 0.021 to 2.317 ± 0.644 mM, 0.409 ± 0.083 to 3.030 ± 0.711 mM against CA‐I and CA‐II, respectively. Each indazole molecule exhibited a noncompetitive inhibition effect. Bromine‐ and chlorine‐bonded indazoles were found to be more potent inhibitory effects on carbonic anhydrase isoenzymes. In conclusion, we conclude that these results may be useful in the synthesis of carbonic anhydrase inhibitors. 相似文献
10.
Suleyman Akocak Parham Taslimi Nebih Lolak Mesut Işık Mustafa Durgun Yakup Budak Cüneyt Türkeş İlhami Gülçin Şükrü Beydemir 《化学与生物多样性》2021,18(4):e2000958
A series of six N-carbamimidoyl-4-(3-substituted phenylureido)benzenesulfonamide derivatives were synthesized by reaction of sulfaguanidine with aromatic isocyanates. In vitro and in silico inhibitory effects of the novel ureido-substituted sulfaguanidine derivatives were investigated by spectrophotometric methods for α-glycosidase (α-GLY), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes associated with diabetes mellitus (DM) and Alzheimer's disease (AD). N-Carbamimidoyl-4-{[(3,4-dichlorophenyl)carbamoyl]amino}benzene-1-sulfonamide ( 2f ) showed AChE and BChE inhibitory effects, with KI values of 515.98±45.03 nM and 598.47±59.18 nM, respectively, while N-carbamimidoyl-4-{[(3-chlorophenyl)carbamoyl]amino}benzene-1-sulfonamide ( 2e ) showed strong α-GLY inhibitory effect, with KI values of 103.94±13.06 nM. The antidiabetic effects of the novel synthesized compounds are higher than their anti-Alzheimer's effects, because the inhibition effect of the compounds on the α-GLY with diabetic enzyme is greater than the effect on esterase enzymes. Indeed, inhibition of the metabolic enzymes is important for the treatment of DM and AD. 相似文献
11.
Mustafa Ceylan Umit M. Kocyigit Necibe Canan Usta Belma Gürbüzlü Yusuf Temel Saleh H. Alwasel İlhami Gülçin 《Journal of biochemical and molecular toxicology》2017,31(4):N/A-N/A
Benzothiazepine compounds have a wide range of applications such as antibacterial, antidepressants, anticonvulsants, antihypertensives, antibiotics, antifungal, hypnotic, enzyme inhibitors, antitumor, anticancer and anti‐HIV agents. In this study, the synthesis of novel tetralone‐based benzothiazepine derivatives ( 1–16 ) and their in vitro antibacterial activity and human carbonic anhydrase isoenzymes I and II (hCA I and II) inhibitory effects were investigated. Both isoenzymes were purified by sepharose‐4B‐l ‐tyrosine‐sulfanilamide affinity chromatography from fresh human red blood cells. All compounds demonstrated the low nanomolar inhibitory effects on both isoenzymes using esterase activity. Benzothiazepine derivative 2 demonstrated the best hCA I inhibitory effect with Ki value of 18.19 nM. Also, benzothiazepine derivative 7 showed the best hCA II inhibitory effect with Ki value of 11.31 nM. On the other hand, acetazolamide clinically used as CA inhibitor, showed Ki value of 19.92 nM against hCA I and 33.60 nM against hCA II, respectively. 相似文献
12.
Murat Bozdag Ahmed Mahmoud Alafeefy Abdul Malik Altamimi Fabrizio Carta Claudiu T. Supuran Daniela Vullo 《Bioorganic & medicinal chemistry》2017,25(10):2782-2788
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 2.7 nM respectively for the hCA IX and KIs 0.57 and 1.9 nM 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. 相似文献
13.
Zübeyir Huyut Şükrü Beydemir İlhami Gülçin 《Journal of biochemical and molecular toxicology》2017,31(9)
Carbonic anhydrases (CAs, E.C.4.2.1.1) play a critical role in many important physiological events and treatment of some diseases. Flavonoids or phenolic compounds have been discovered as novel CAs inhibitors instead of the traditional sulfonamides, with different binding to CAs, pro‐drug activities, and new inhibition mechanisms. Here, we investigated the inhibition effects of some flavonoids including malvin, callistephin, oenin, pelargonin, silychristin, and 1‐(4‐methoxyphenyl)‐2‐methyl‐3‐nitro‐1‐H‐indol‐6‐ol (ID‐8) against hCA I and II, which purified from human erythrocytes by affinity column chromatography. Both hCA isoenzymes were inhibited by flavonoids, with IC50 and Ki values in the range of 2.34 nM to 346.5 μM and 51.01–99.55 μM for hCA I and 86.60–750.00 μM for hCA II, respectively. These results showed that flavonoids especially malvin and oenin effectively inhibited hCA I and II isoenzymes. Hence, they may be used as an effective CA inhibitor in medical applications for treatment of certain diseases such as glaucoma, in the future. 相似文献
14.
Süleyman Yılmaz Yusuf Akbaba Bünyamin Özgeriş Leyla Polat Köse 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1484-1491
A series of carbamate derivatives were synthesized and their carbonic anhydrase I and II isoenzymes and acetylcholinesterase enzyme (AChE) inhibitory effects were investigated. All carbamates were synthesized from the corresponding carboxylic acids via the Curtius reactions of the acids with diphenyl phosphoryl azide followed by addition of benzyl alcohol. The carbamates were determined to be very good inhibitors against for AChE and hCA I, and II isoenzymes. AChE inhibition was determined in the range 0.209–0.291?nM. On the other hand, tacrine, which is used in the treatment of Alzheimer’s disease possessed lower inhibition effect (Ki: 0.398?nM). Also, hCA I and II isoenzymes were effectively inhibited by the carbamates, with inhibition constants (Ki) in the range of 4.49–5.61?nM for hCA I, and 4.94–7.66?nM for hCA II, respectively. Acetazolamide, which was clinically used carbonic anhydrase (CA) inhibitor demonstrated Ki values of 281.33?nM for hCA I and 9.07?nM for hCA II. The results clearly showed that AChE and both CA isoenzymes were effectively inhibited by carbamates at the low nanomolar levels. 相似文献
15.
Synthesis and investigation of the conversion reactions of pyrimidine‐thiones with nucleophilic reagent and evaluation of their acetylcholinesterase,carbonic anhydrase inhibition,and antioxidant activities
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Parham Taslimi Afsun Sujayev Fikret Turkan Emin Garibov Zübeyir Huyut Vagif Farzaliyev Sevgi Mamedova İlhami Gulçin 《Journal of biochemical and molecular toxicology》2018,32(2)
The conversion reactions of pyrimidine‐thiones with nucleophilic reagent were studied during this scientific research. For this purpose, new compounds were synthesized by the interaction between 1,2‐epoxy propane, 1,2‐epoxy butane, and 4‐chlor‐1‐butanol and pyrimidine‐thiones. These pyrimidine‐thiones derivatives ( A–K ) showed good inhibitory action against acetylcholinesterase (AChE), and human carbonic anhydrase (hCA) isoforms I and II. AChE inhibition was in the range of 93.1 ± 33.7–467.5 ± 126.9 nM. The hCA I and II were effectively inhibited by these compounds, with Ki values in the range of 4.3 ± 1.1–9.1 ± 2.7 nM for hCA I and 4.2 ± 1.1–14.1 ± 4.4 nM for hCA II. On the other hand, acetazolamide clinically used as CA inhibitor showed Ki value of 13.9 ± 5.1 nM against hCA I and 18.1 ± 8.5 nM against hCA II. The antioxidant activity of the pyrimidine‐thiones derivatives ( A–K ) was investigated by using different in vitro antioxidant assays, including Cu2+ and Fe3+ reducing, 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH?) radical scavenging, and Fe2+ chelating activities. 相似文献
16.
In this work, the inhibitory activity of Voriconazole was measured against some metabolic enzymes, including human carbonic anhydrase (hCA) I and II isoenzymes, acetylcholinesterase (AChE), and α‐glycosidase; the results were compared with standard compounds including acetazolamide, tacrine, and acarbose. Half maximal inhibition concentration (IC50) values were obtained from the enzyme activity (%)‐[Voriconazole] graphs, whereas Ki values were calculated from the Lineweaver‐Burk graphs. According to the results, the IC50 value of Voriconazole was 40.77 nM for α‐glycosidase, while the mean inhibition constant (Ki) value was 17.47 ± 1.51 nM for α‐glycosidase. The results make an important contribution to drug design and have pharmacological applications. In addition, the Voriconazole compound demonstrated excellent inhibitory effects against AChE and hCA isoforms I and II. Voriconazole had Ki values of 29.13 ± 3.57 nM against hCA I, 15.92 ± 1.90 nM against hCA II, and 10.50 ± 2.46 nM against AChE. 相似文献
17.
A novel class of fluoro-substituted tris-chalcones derivatives (5a-5i) was synthesized from phloroglucinol and corresponding benzaldehydes. A three step synthesis method was followed for the production of these tris-chalcone compounds. The structures of the newly synthesized compounds (5a-5i) were confirmed on the basis of IR, 1H NMR, 13C NMR, and elemental analysis. The compounds’ inhibitory activities were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly). These chalcone derivatives had Ki values in the range of 19.58–78.73 nM for hCA I, 12.23–41.70 nM for hCA II, 1.09–6.84 nM for AChE, 8.30–32.30 nM for BChE and 0.93 ± 0.20–18.53 ± 5.06 nM against α-glycosidase. These results strongly support the promising nature of the tris-chalcone scaffold as selective carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase inhibitor. Overall, due to these derivatives’ inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer’s disease; type-2 diabetes mellitus that are associated with high enzymatic activity of carbonic anhydrase, acetylcholine esterase, butyrylcholinesterase, and α-glycosidase. 相似文献
18.
Enantioselective synthesis of functionalized cyclic allylic alcohols via kinetic resolution in transesterifcation with different lipase enzymes has been developed. The influence of the enzymes and temperature activity was studied. By determination of ideal reaction conditions, byproduct formation is minimized; this made it possible to prepare enantiomerically enriched allylic alcohols in high ee's and good yields. Enantiomerically enriched allylic alcohols were used for enantiomerically enriched oxazolidinone synthesis. Using benzoate as a leaving group means that 1 mol % of potassium osmate is necessary and can be obtained high yields 98%. Inhibitory activities of enantiomerically enriched oxazolidinones (8, 10 and 12) were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and α-glycosidase (α-Gly) enzymes. These enantiomerically enriched oxazolidinones derivatives had Ki values in the range of 11.6 ± 2.1–66.4 ± 22.7 nM for hCA I, 34.1 ± 6.7–45.2 ± 12.9 nM for hCA II, 16.5 ± 2.9 to 35.6 ± 13.9 for AChE, and 22.3 ± 6.0–70.9 ± 9.9 nM for α-glycosidase enzyme. Moreover, they had high binding affinity with −5.767, −6.568, −9.014, and −8.563 kcal/mol for hCA I, hCA II, AChE and α-glycosidase enzyme, respectively. These results strongly supported the promising nature of the enantiomerically enriched oxazolidinones as selective hCA, AChE, and α-glycosidase inhibitors. Overall, due to these derivatives’ inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer’s disease; type-2 diabetes mellitus that are associated with high enzymatic activity of CA, AChE, and α-glycosidase. 相似文献
19.
《Bioorganic & medicinal chemistry》2016,24(6):1402-1407
A series of heterocyclic benzenesulfonamides incorporating 2-mercapto-3H-quinazolin-4-one tails were prepared by condensation of substituted anthranilic acids with 4-isothiocyanato-benzenesulfonamide. 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 IX and XII (trans-membrane, tumor-associated enzymes). They acted as medium potency inhibitors of hCA I (KIs of 81.0–3084 nM), being highly effective as hCA II (KIs in the range of 0.25–10.8 nM), IX (KIs of 3.7–50.4 nM) and XII (KIs of 0.60–52.9 nM) 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 three isoforms (CA II, IX and XII) is dysregulated. 相似文献
20.
Mona F. Said Riham F. George Andrea Petreni Claudiu T. Supuran Nada M. Mohamed 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):701
In continuation of our previous studies to optimise potent carbonic anhydrase inhibitors, two new series of isatin N-phenylacetamide based sulphonamides were synthesised and screened for their human (h) carbonic anhydrase (EC 4.2.1.1) inhibitory activities against four isoforms hCA I, hCA II, hCA IX and hCA XII. The indole-2,3-dione derivative 2h showed the most effective inhibition profile against hCAI and hCA II (KI = 45.10, 5.87 nM) compared to acetazolamide (AAZ) as standard inhibitor. Moreover, 2h showed appreciable inhibition activity against the tumour-associated hCA XII, similar to AAZ showing KI of 7.91 and 5.70 nM, respectively. The analogs 3c and 3d showed good cytotoxicity effects, and 3c revealed promising selectivity towards lung cell line A549. Molecular docking was carried out for 2h and 3c to predict their binding conformations and affinities towards the hCA I, II, IX and XII isoforms. 相似文献