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1.
Medicina (Kaunas) ; 58(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36143982

RESUMO

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.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos
2.
3.
RSC Adv ; 11(52): 33081, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-35503265

RESUMO

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

4.
Bioorg Chem ; 77: 101-105, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29353727

RESUMO

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.


Assuntos
Acridinas/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/farmacologia , Tiadiazóis/farmacologia , Acridinas/química , Anidrase Carbônica I/antagonistas & inibidores , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/metabolismo , Anidrase Carbônica IV/antagonistas & inibidores , Anidrase Carbônica IV/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Tiadiazóis/síntese química , Tiadiazóis/química
5.
Bioorg Chem ; 70: 245-255, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28153340

RESUMO

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.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Tacrina/análogos & derivados , Tacrina/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Animais , Antioxidantes/síntese química , Benzotiazóis/química , Compostos de Bifenilo/química , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/síntese química , Electrophorus , Radicais Livres/química , Cavalos , Humanos , Micro-Ondas , Picratos/química , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia , Ácidos Sulfônicos/química , Tacrina/síntese química
6.
Bioorg Med Chem Lett ; 27(1): 86-89, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27876475

RESUMO

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.


Assuntos
Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Micro-Ondas , Sulfonamidas/farmacologia , Tetrazóis/farmacologia , Acridinas/química , Acridinas/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Tetrazóis/síntese química , Tetrazóis/química , Xantenos/química , Xantenos/farmacologia
7.
J Enzyme Inhib Med Chem ; 31(6): 1356-61, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27541741

RESUMO

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.


Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/síntese química , Sulfonamidas/síntese química , Inibidores da Anidrase Carbônica/farmacologia , Eritrócitos/enzimologia , Humanos , Concentração Inibidora 50 , Análise Espectral/métodos , Sulfonamidas/farmacologia
8.
J Nanosci Nanotechnol ; 16(6): 6498-504, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27427743

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-27298005

RESUMO

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.


Assuntos
Acetazolamida/química , Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Isoenzimas/efeitos dos fármacos , Micro-Ondas , Inibidores da Anidrase Carbônica/química , Humanos , Análise Espectral/métodos
10.
J Enzyme Inhib Med Chem ; 31(sup2): 63-69, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27237188

RESUMO

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.


Assuntos
Acridinas/farmacologia , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Sulfaguanidina/farmacologia , Acridinas/química , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Cromatografia de Afinidade , Relação Dose-Resposta a Droga , Eritrócitos/enzimologia , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Sulfaguanidina/química
11.
J Enzyme Inhib Med Chem ; 31(6): 1005-10, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26327456

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bacillus/efeitos dos fármacos , Enterobacter aerogenes/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Sulfonamidas/síntese química , Sulfonamidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/química
12.
Bioorg Med Chem ; 23(20): 6573-80, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26422787

RESUMO

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.


Assuntos
Antígenos de Neoplasias/metabolismo , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Anidrase Carbônica IX , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
13.
Bioorg Med Chem ; 21(18): 5799-805, 2013 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-23910989

RESUMO

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.


Assuntos
Acridinas/química , Anidrase Carbônica II/antagonistas & inibidores , Inibidores da Anidrase Carbônica/síntese química , Anidrases Carbônicas/química , Sulfonamidas/química , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/metabolismo , Anidrases Carbônicas/metabolismo , Humanos , Cinética , Ligação Proteica , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/metabolismo , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/metabolismo
14.
J Enzyme Inhib Med Chem ; 28(5): 885-93, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22803669

RESUMO

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.


Assuntos
Amidas/farmacologia , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Xantenos/farmacologia , Amidas/síntese química , Amidas/química , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química , Sulfonamidas/farmacologia , Xantenos/síntese química , Xantenos/química
15.
J Enzyme Inhib Med Chem ; 27(4): 509-14, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21846203

RESUMO

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.


Assuntos
Acridinas/farmacologia , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Sulfonamidas/farmacologia , Acridinas/síntese química , Acridinas/química , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/síntese química , Sulfonamidas/química
16.
J Zhejiang Univ Sci B ; 9(5): 371-7, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18500776

RESUMO

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.


Assuntos
Cicer/crescimento & desenvolvimento , Plântula/crescimento & desenvolvimento , Sementes/anatomia & histologia , Cloreto de Sódio/farmacologia , Modelos Lineares , Sementes/fisiologia
17.
Acta Crystallogr Sect E Struct Rep Online ; 64(Pt 4): o681, 2008 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-21202073

RESUMO

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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