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1.
Medicina (Kaunas) ; 58(9)2022 Sep 19.
Article in English | MEDLINE | ID: mdl-36143982

ABSTRACT

Background and Objectives: The survival benefit of anatomical liver resection for hepatocellular carcinoma has not been elucidated yet. In this study, we aimed to investigate the effects of anatomic and non-anatomic liver resection on surgical outcomes in patients with hepatocellular carcinoma. Materials and Methods: A retrospective analysis of patients undergoing anatomic or non-anatomic resections due to hepatocellular carcinoma between March 2006 and October 2019 was conducted. Demographics, preoperative laboratory assessments, treatment strategies, and postoperative outcomes were analyzed. Results: The total cohort consisted of 94 patients, with a mean age of 63.1 ± 8.9 years, and 74.5% were male. A total of 41 patients underwent anatomic liver resection, and 53 patients underwent non-anatomic resection. The overall survival rates were found to be similar (5-year overall survival was 49.3% for anatomic resection and 44.5% for non-anatomic resection). Estimated median overall survival times were 58.5 months and 57.3 months, respectively (p = 0.777). Recurrence-free 1-, 3-, and 5-year survival rates were found to be 73.6%, 39.1%, and 32.8% in the non-anatomic resection group and 48.8%, 22.7%, and 22.7% in the anatomic resection group, respectively. Grade three or higher complication rates were found to be similar among the groups. Conclusions: This study did not find a difference between two surgical methods, in terms of survival. A tailored selection of the resection method should be made, with the aim of complete removal of tumoral lesions and leaving a suitable functional liver reserve, according to the parenchymal quality and volume of the liver remnant.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Aged , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/surgery , Cohort Studies , Female , Humans , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies
2.
RSC Adv ; 11(52): 33082, 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-35503262

ABSTRACT

[This retracts the article DOI: 10.1039/C5RA11426H.].

3.
RSC Adv ; 11(52): 33081, 2021 Oct 04.
Article in English | MEDLINE | ID: mdl-35503265

ABSTRACT

[This retracts the article DOI: 10.1039/C5RA06441D.].

4.
Bioorg Chem ; 77: 101-105, 2018 04.
Article in English | MEDLINE | ID: mdl-29353727

ABSTRACT

Herein, we report that acridine intermediates 5 were obtained from the reduction of nitro acridine derivatives 4, which were synthesized via condensation of dimedone, p-nitrobenzaldehyde with 4-amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide, respectively. Then acridine sulfonamide/carboxamide (7a-i) compounds were synthesized by reaction of amino acridine 5 with sulfonyl chlorides and carbamoyl chlorides. The new compounds were characterized by melting points, FT-IR, 1H NMR, 13C NMR and HRMS analyzes. The evaluation of in vitro test of the synthesized compounds against hCA I, II, IV and VII showed that some of them are potent inhibitors. Among them, compound 7e showed the most potent activity against hCA II with a KI of 7.9 nM.


Subject(s)
Acridines/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Sulfonamides/pharmacology , Thiadiazoles/pharmacology , Acridines/chemistry , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase IV/antagonists & inhibitors , Carbonic Anhydrase IV/metabolism , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrases/metabolism , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Thiadiazoles/chemical synthesis , Thiadiazoles/chemistry
5.
Bioorg Chem ; 70: 245-255, 2017 02.
Article in English | MEDLINE | ID: mdl-28153340

ABSTRACT

A novel series of tacrine derivatives containing sulfonamide group were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized tacrine-sulfonamides (VIIIa-o) exhibited inhibitory activity on both cholinesterases. VIIIg showed the highest inhibitory activity on AChE IC50=0.009µM. This value is 220-fold greater than that of galantamine (IC50=2.054µM) and 6-fold greater than tacrine (IC50=0.055µM). VIIIf displayed the strongest inhibition of BuChE (IC50=2.250µM), which is close to donepezil (IC50=2.680µM) and 8-fold greater than that of galantamine (IC50=18.130µM) Furthermore, all of the synthesized tacrine derivatives showed higher inhibition of BuChE than that of galantamine. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for the antioxidant activity. Among them, VIIIb (IC50=94.390±2.310µM) showed significantly better ABTS cation radical scavenging ability than all of the new synthesized compounds.


Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Cholinesterase Inhibitors/chemistry , Cholinesterase Inhibitors/pharmacology , Tacrine/analogs & derivatives , Tacrine/pharmacology , Acetylcholinesterase/metabolism , Alzheimer Disease/drug therapy , Alzheimer Disease/enzymology , Animals , Antioxidants/chemical synthesis , Benzothiazoles/chemistry , Biphenyl Compounds/chemistry , Butyrylcholinesterase/metabolism , Cholinesterase Inhibitors/chemical synthesis , Electrophorus , Free Radicals/chemistry , Horses , Humans , Microwaves , Picrates/chemistry , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Sulfonamides/pharmacology , Sulfonic Acids/chemistry , Tacrine/chemical synthesis
6.
Bioorg Med Chem Lett ; 27(1): 86-89, 2017 01 01.
Article in English | MEDLINE | ID: mdl-27876475

ABSTRACT

The synthesis of novel tetrazole/sulfonamide derivatives based on octahydroacridine, xanthene and chromene scaffold by using microwave (MW) assisted techniques is reported in this study. These synthesized hybrid compounds were assayed for the inhibition of carbonic anhydrase (CA, EC 4.2.1.1). The inhibitory activities were determined against three cytosolic human isoforms (hCA I, II and VII) and one membrane-associated (hCA IV) isoform. Some of the newly synthesized sulfonamides showed micromolar to nanomolar inhibitory activity against these enzymes.


Subject(s)
Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/metabolism , Microwaves , Sulfonamides/pharmacology , Tetrazoles/pharmacology , Acridines/chemistry , Acridines/pharmacology , Benzopyrans/chemistry , Benzopyrans/pharmacology , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Tetrazoles/chemical synthesis , Tetrazoles/chemistry , Xanthenes/chemistry , Xanthenes/pharmacology
7.
J Enzyme Inhib Med Chem ; 31(6): 1356-61, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27541741

ABSTRACT

Novel sulfonamide derivatives 6a-i, as new carbonic anhydrase inhibitors which candidate for glaucoma treatment, were synthesized from the reactions of 4-amino-N-(4-sulfamoylphenyl) benzamide 4 and sulfonyl chloride derivatives 5a-i with high yield (71-90%). The structures of these compounds were confirmed by using spectral analysis (FT-IR, (1)H NMR, (13)C NMR, LC/MS and HRMS). The inhibition effects of 6a-i on the hydratase and esterase activities of human carbonic anhydrase isoenzymes, hCA I and II, which were purified from human erythrocytes with Sepharose®4B-l-tyrosine-p-aminobenzene sulfonamide affinity chromatography, were studied as in vitro, and IC50 and Ki values were determined. The results show that newly synthesized compounds have quite powerful inhibitory properties.


Subject(s)
Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/chemical synthesis , Sulfonamides/chemical synthesis , Carbonic Anhydrase Inhibitors/pharmacology , Erythrocytes/enzymology , Humans , Inhibitory Concentration 50 , Spectrum Analysis/methods , Sulfonamides/pharmacology
8.
J Nanosci Nanotechnol ; 16(6): 6498-504, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27427743

ABSTRACT

Graphene oxide as a highly stable, reusable, isolable, and efficient catalyst has been used for the first time for the synthesis of acridinedione derivatives from dimedone, aromatic aldehydes and various amines with great catalytic performance. One pot synthesis of acridinedione compounds were performed using highly efficient graphene oxide.

9.
Bioorg Med Chem ; 24(16): 3548-55, 2016 08 15.
Article in English | MEDLINE | ID: mdl-27298005

ABSTRACT

4-Amino-N-(5-sulfamoyl-1,3,4-thiadiazol-2-yl)benzamide was condensed with cyclic-1,3-diketones (dimedone and cyclohexane-1,3-dione) and aromatic aldehydes under microwave irradiation, leading to a series of acridine-acetazolamide conjugates. The new compounds were investigated as inhibitors of carbonic anhydrases (CA, EC 4.2.1.1), and more precisely cytosolic isoforms hCA I, II, VII and membrane-bound one hCA IV. All investigated isoforms were inhibited in low micromolar and nanomolar range by the new compounds. hCA IV and VII were inhibited with KIs in the range of 29.7-708.8nM (hCA IV), and of 1.3-90.7nM (hCA VII). For hCA I and II the KIs were in the range of 6.7-335.2nM (hCA I) and of 0.5-55.4nM (hCA II). The structure-activity relationships (SAR) for the inhibition of these isoforms with the acridine-acetazolamide conjugates reported here were delineated.


Subject(s)
Acetazolamide/chemistry , Acetazolamide/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Isoenzymes/drug effects , Microwaves , Carbonic Anhydrase Inhibitors/chemistry , Humans , Spectrum Analysis/methods
10.
J Enzyme Inhib Med Chem ; 31(sup2): 63-69, 2016.
Article in English | MEDLINE | ID: mdl-27237188

ABSTRACT

Novel sulfaguanidines incorporating acridine moiety were synthesized by the reaction of cyclohexane-1,3-dione, sulfaguanidine, and aromatic aldehydes. Synthesis of these compounds was performed in water at room temperature, and their structures were confirmed by using spectral analysis (IR, 1H-NMR, 13C-NMR, and HRMS). Human carbonic anhydrase isoenzymes (hCA I and II) were purified from erythrocyte cells with affinity chromatography. hCA I was purified 83.40-fold with a specific activity, 1060.9 EU mg protein-1, and hCA II was purified 262.32-fold with a specific activity, 3336.8 EU mg protein-1. The inhibitory effects of newly synthesized sulfaguanidines and acetazolamide, (AAZ) as a control compound, on hydratase and esterase activities of these isoenzymes have been studied in vitro. Synthesized compounds have moderate inhibition potentials on hCA I and hCA II isoenzymes. IC50 values of compounds for esterase activity are in the range of 118.4 ± 7.0 µM-257.5 ± 5.2 µM for hCA I and 86.7 ± 3.0 µM-249.4 ± 10.2 µM for hCA II, respectively.


Subject(s)
Acridines/pharmacology , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/pharmacology , Sulfaguanidine/pharmacology , Acridines/chemistry , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Chromatography, Affinity , Dose-Response Relationship, Drug , Erythrocytes/enzymology , Humans , Isoenzymes/antagonists & inhibitors , Isoenzymes/metabolism , Molecular Structure , Structure-Activity Relationship , Sulfaguanidine/chemistry
11.
J Enzyme Inhib Med Chem ; 31(6): 1005-10, 2016 Dec.
Article in English | MEDLINE | ID: mdl-26327456

ABSTRACT

Sulfamerazine and sulfaguanidine are clenched with p-nitrobenzoyl chloride and the products obtained are reduced to NaxS in ethanol-water. Novel sulfonamides (6a-g and 9a-g) were synthesized by the reaction of these reduced products (4 and 8) with various sulfonyl chlorides (5a-g). The structures of these compounds were characterized using spectroscopic analysis (IR, (1)H-NMR, (13)C-NMR and HRMS) technique. Antimicrobial activity of sulfonamides (3, 4, 7, 8, 6a-g and 9a-g) was evaluated by the agar diffusion method. These compounds showed antimicrobial activity against tested microorganism strains (Gram-positive bacteria, clinic isolate and yeast and mold). Compounds 9d, 9e, 9a, 6d and 6e showed particularly antimicrobial activity against tested Gram-positive (Bacillus cereus and B. subtilis) and Gram-negative (Enterobacter aerogenes) bacteria.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacillus/drug effects , Enterobacter aerogenes/drug effects , Saccharomyces cerevisiae/drug effects , Sulfonamides/chemical synthesis , Sulfonamides/pharmacology , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemistry
12.
Bioorg Med Chem ; 23(20): 6573-80, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26422787

ABSTRACT

By using a multi component reaction system (MCR), nitro acridine sulfonamides were obtained from cyclic-1,3-diketones, 4-aminobenzene sulfonamide and aromatic aldehydes. Some novel acridine bis-sulfonamides 6a-l were then synthesized by the reaction between sulfonyl chlorides and the novel amino-acridine sulfonamides 5a and 5b, obtained by reduction of nitro-acridine sulfonamide derivatives 4a and 4b. The newly synthesized compounds were investigated as inhibitors of 4 human carbonic anhydrase isoforms (hCA, EC 4.2.1.1). Several of the compounds showed low micromolar inhibition against the medically relevant isoforms hCA I, II, IX, and XII.


Subject(s)
Antigens, Neoplasm/metabolism , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/pharmacology , Carbonic Anhydrases/metabolism , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase IX , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship
13.
Bioorg Med Chem ; 21(18): 5799-805, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-23910989

ABSTRACT

4-Amino-N-(4-sulfamoylphenyl)benzamide was synthesized by reduction of 4-nitro-N-(4-sulfamoylphenyl)benzamide and used to synthesize novel acridine sulfonamide compounds, by a coupling reaction with cyclic-1,3-diketones and aromatic aldehydes. The new compounds were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely the cytosolic isoforms hCA I, II and VII. hCA I was inhibited in the micromolar range by the new compounds (KIs of 0.16-9.64 µM) whereas hCA II and VII showed higher affinity for these compounds, with KIs in the range of 15-96 nM for hCA II, and of 4-498 nM for hCA VII. The structure-activity relationships for the inhibition of these isoforms with the acridine-sulfonamides reported here were also elucidated.


Subject(s)
Acridines/chemistry , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrases/chemistry , Sulfonamides/chemistry , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/metabolism , Carbonic Anhydrases/metabolism , Humans , Kinetics , Protein Binding , Protein Isoforms/antagonists & inhibitors , Protein Isoforms/metabolism , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/metabolism
14.
J Enzyme Inhib Med Chem ; 28(5): 885-93, 2013 Oct.
Article in English | MEDLINE | ID: mdl-22803669

ABSTRACT

Xanthene intermediates 4a and 4b were obtained from the reduction of nitro xanthene derivatives 3a and 3b which were synthesized via condensation of dimedone with m-nitrobenzaldehyde and p-nitrobenzaldehyde, respectively. Then xanthene sulfonamide 6a-n, and xanthene carboxamide derivatives 8a-h were synthesized by reaction of amino xanthene 4a, 4b with sulfonyl chlorides 5a-g and acyl chlorides 7a-d. Structures of the novel amino xanthene compounds and xanthene sulfonamide/carboxamide derivatives were established by their spectral data and elemental analyses. Furthermore, all the synthesized compounds were tested in vitro for their antimicrobial activity. The results were compared with reference standard antibiotics, erythromycin and nystatin. 6c, 6f, 6m and 8b Compounds were found to display most effective antimicrobial activity against a series of bacteria and fungi.


Subject(s)
Amides/pharmacology , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Fungi/drug effects , Xanthenes/pharmacology , Amides/chemical synthesis , Amides/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Dose-Response Relationship, Drug , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry , Sulfonamides/pharmacology , Xanthenes/chemical synthesis , Xanthenes/chemistry
15.
J Enzyme Inhib Med Chem ; 27(4): 509-14, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21846203

ABSTRACT

Novel dioxoacridine sulfonamide compounds were synthesized from reaction of cyclic 1,3-diketones, sulfanilamide (4-amino benzene sulfonamide) and aromatic aldehydes. The structures of these compounds were confirmed by using spectral analysis (IR, H-NMR, (13)C-NMR, and mass). Human carbonic anhydrase isoenzymes (hCA I and hCA II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of sulfanilamide, acetazolamide (AAZ), and newly synthesized sulfonamides on hydratase and esterase activities of these isoenzymes have been studied in vitro. The IC(50) values of compounds for esterase activity are 0.71-0.11 µM for hCA I and 0.45-0.12 µM for hCA II, respectively. The K(i) values of these inhibitors were determined as 0,38-0,008 µM for hCA I and 0,19-0,001 µM for hCA II, respectively.


Subject(s)
Acridines/pharmacology , Carbonic Anhydrase II/antagonists & inhibitors , Carbonic Anhydrase I/antagonists & inhibitors , Carbonic Anhydrase Inhibitors/pharmacology , Sulfonamides/pharmacology , Acridines/chemical synthesis , Acridines/chemistry , Carbonic Anhydrase I/metabolism , Carbonic Anhydrase II/metabolism , Carbonic Anhydrase Inhibitors/chemical synthesis , Carbonic Anhydrase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemical synthesis , Sulfonamides/chemistry
16.
J Zhejiang Univ Sci B ; 9(5): 371-7, 2008 May.
Article in English | MEDLINE | ID: mdl-18500776

ABSTRACT

Chickpea is an important food legume crop of Turkey and is largely grown for human consumption on low moisture or salt-affected soils. The objective of the study was to find the effects of NaCl stress at electrical conductivities of 4.5, 8.6, 12.7 and 16.3 dS/m and seed sizes (7, 8 and 9 mm) on germination and early seedling growth of three popular chickpea cultivars (AKN-97, Gokce and Uzunlu-99). Mean frequency of germination, germination time, germination index, root length, shoot length and seedling fresh weight showed seed size-dependent responses of cultivars to salt stress. In general, small seeds germinated and grew more rapidly compared to medium and large seeds of the same cultivars against all levels of salt stress, with the best results in cultivar Uzunlu-99. No effect of NaCl treatments was observed on frequency of germination; however, a drastic decrease in early seedling growth was recorded at increased NaCl concentrations. Regression analysis results showed a significantly positive relationship (P<0.01) between seed size and mean germination time, whereas a significantly negative relationship was recorded between seed size and germination index, root length, shoot length. Moreover, linear regression values apparently confirmed that increased seed size in each cultivar affected decreased germination index, root and shoot lengths with enhanced mean germination time. Thus, it was concluded that the use of small seeds could considerably reduce the production costs of chickpea in salt-affected soils.


Subject(s)
Cicer/growth & development , Seedlings/growth & development , Seeds/anatomy & histology , Sodium Chloride/pharmacology , Linear Models , Seeds/physiology
17.
Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 4): o681, 2008 Mar 07.
Article in English | MEDLINE | ID: mdl-21202073

ABSTRACT

In the mol-ecule of the title compound, C(24)H(28)O(4), the three six-membered rings of the xanthene system are not planar, having envelope, boat and envelope conformations. In the crystal structure, C-H⋯O hydrogen bonds link the mol-ecules, generating centrosymmetric R(2) (2)(12), R(4) (4)(28) and R(2) (2)(16) ring motifs and forming a three-dimensional network.

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