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1.
Bioorg Chem ; 92: 103262, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518757

RESUMO

This report presents the development of a novel and primary model of sulfonamide compounds encompassing a chromene azo motif with the intent of becoming applicable for drug candidates in the cases of drug-resistant pathogens. The novel molecules (7a-n) have been synthesized via a two-step reaction. First, 4-((2, 4-dihydroxyphenyl)diazenyl)benzenesulfonamide (3a-e) were obtained through the reaction of their corresponding diazotized 4-aminobenzenesulfonamides (1a-e) with resorcinol, followed by the heterocyclization of 3a-e with arylidenemalononitriles (6a-d). Upon structural identification, the newly synthesized compounds were evaluated for their antibacterial and antifungal activities. Moreover, their cytotoxic screening was performed against three cancer cell lines: HCT-116, HepG-2, and MCF-7. Further examinations were comprised of the inhibitory effect analyses of the novel sulfonamide/chromene derivatives against the HDAC classes and the Tubulin polymerization in order to discern the prime antitumor drug candidates.

2.
Chem Cent J ; 11(1): 32, 2017 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-29086809

RESUMO

BACKGROUND: Various thiourea derivatives have been used as starting materials for compounds with better biological activities. Molecular modeling tools are used to explore their mechanism of action. RESULTS: A new series of thioureas were synthesized. Fluorinated pyridine derivative 4a showed the highest antimicrobial activity (with MIC values ranged from 1.95 to 15.63 µg/mL). Interestingly, thiadiazole derivative 4c and coumarin derivative 4d exhibited selective antibacterial activities against Gram positive bacteria. Fluorinated pyridine derivative 4a was the most active against HepG2 with IC50 value of 4.8 µg/mL. Molecular docking was performed on the active site of MK-2 with good results. CONCLUSION: Novel compounds were obtained with good anticancer and antibacterial activity especially fluorinated pyridine derivative 4a and molecular docking study suggest good activity as mitogen activated protein kinase-2 inhibitor. Graphical abstract Compound 4a in the active site of MK-2.

3.
Chem Cent J ; 11(1): 42, 2017 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-29086825

RESUMO

BACKGROUND: A series of novel N-(2, 6-dimethoxypyrimidin-4-yl)-4-(3-(aryl)thioureido) benzenesulfonamides 3a-t was synthesized by the addition of N-(2,6-dimethoxypyrimidin-4-yl)-4-isothiocyanatobenzenesulfonamide 2 to the appropriate aromatic amine. The structures of the synthesized compounds were inspired from the second line antituberculosis pro-drugs. RESULTS: Most of the new compounds were screened for their activity against Mycobacterium tuberculosis. The results of the antimycobacterial assay showed that compound 3i exerted the highest activity (MIC = 3.13 µg/mL), followed by compound 3s (MIC = 6.25 µg/mL). CONCLUSION: The structure-activity relationship (SAR) analysis revealed that the introduction of the benzo[1,3]dioxol moiety in 3i and the 4-morpholinyl-4-phenyl moiety in 3s has proven to give the most potent compounds in this study. Docking of the promising compounds inside the active site of M. tuberculosis enoyl reductase InhA was performed in order to emphasize the results. The compounds showed a similar orientation to that of GSK 625 inside the active site of 5JFO and bind to Met 98 in a way similar to that of the co-crystallized ligand.

4.
Anticancer Agents Med Chem ; 17(10): 1411-1425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28356021

RESUMO

BACKGROUND: Thiourea derivatives bearing sulfonamide moiety are well known for their anticancer activity. OBJECTIVE: The anticancer activity of the target compounds was studied, via inhibition of COX-2 enzyme. METHOD: A series of novel thioureas 5a-n, 8, quinazoline 6, benzo[g]quinazoline 7 and benzo[1,3] dioxole 10, bearing a sulfonamide moiety was synthesized from the starting compound N-(2,6-dimethoxypyrimidin-4-yl)-4- isothiocyanatobenzenesulfonamide 2. The target compounds were screened against HepG2, MCF-7, Caco-2, HCT-116, PC-3 cancer cell lines and VERO-B normal cell line. RESULTS: Out of all the tested compounds, compound 5c showed a broad selective cytotoxicity against HepG2, MCF-7, Caco-2 and PC-3 cancer cells. Moreover, a sensitization assay was performed on Caco-2 cells, and compound 5c proved to act as a chemosensitizer for cisplatin on colon cancer (Caco-2) cells. The target compounds were further screened in vitro for their anti COX1/COX2 activity and investigated in vivo as antiinflammatory agents against carrageenan-induced rat paw oedema model. CONCLUSION: Compound 5g showed the most selective inhibitory activity against COX-2. While, compounds 5a, 6, 5m, 5n, 5g and 5i revealed significant anti-inflammatory effect as presented in carrageenan-induced oedema assay. Molecular docking of the tested compounds disclosed important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/metabolismo , Sulfonamidas/farmacologia , Tioureia/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Sulfonamidas/química , Tioureia/síntese química , Tioureia/química
5.
Eur J Med Chem ; 124: 299-310, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27597407

RESUMO

A series of novel heterocyclic thioureas 3a-u containing sulfonamide moiety have been synthesized by the condensation of isothiocyanatobenzenesulfonamide 2 with a variety of heterocyclic amines. The newly synthesized heterocyclic thioureas were investigated for their antimicrobial and anticancer activity. The in vitro antibacterial and antifungal activity were done using well diffusion method. Interestingly, compounds 3j and 3m, showed similar or better activity compared with the reference drug against the tested microorganisms. Although, 3j was less active among its analogues to inhibit the breast carcinoma cells, it exhibit strong broad spectrum antimicrobial activities. However, The results of the cytotoxic activity revealed that compound 3p was the most active against the breast carcinoma cell line (MCF-7) giving promising IC50 value of 1.72 µg/mL, compared with reference drug (5-flourouracil) with IC50 value of 4.8 µg/mL. The most potent compounds in cytotoxic activity 3b and 3p were further docked inside the active site of CAIX and were found to exhibit a proper binding with the active site amino acids according to their bond lengths, angles and conformational energy.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Tioureia/química , Anti-Infecciosos/metabolismo , Antígenos de Neoplasias/química , Antígenos de Neoplasias/metabolismo , Antineoplásicos/metabolismo , Anidrase Carbônica IX/química , Anidrase Carbônica IX/metabolismo , Domínio Catalítico , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Sulfonamidas/metabolismo
6.
Eur J Med Chem ; 44(10): 4148-52, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19540629

RESUMO

2-Thioxo-4-thiazolidinones (3a,b) were achieved by cyclocondensation of isothiocyanatosulfonamides (1a,b) with sulfanylacetic acid at reflux temperature in dioxane in the presence of triethylamine. Compound (3a) was exploited to synthesize the versatile hitherto unknown 2-thioxo-4-thiazolidinones (5-10) via its reaction with some electrophiles. Cyclization of 4,4'-diisothiocyanate diphenylsulfone (11) with sulfanylacetic acid furnished 4,4'-bis(2-thioxo-4-thiazolidinone-3-yl)diphenylsulfone (12) which on treatment with excess 4-methoxybenzaldehyde in refluxing dioxane in the presence of piperidine yielded the bisbenzylidene derivative (13). The novel synthesized compounds were characterized by IR, (1)H NMR and mass spectral studies. All the synthesized compounds were screened in vitro for their antibacterial and antifungal activities.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Isotiocianatos/química , Isotiocianatos/farmacologia , Tiazolidinas/química , Tiazolidinas/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Isotiocianatos/síntese química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinas/síntese química
7.
Arzneimittelforschung ; 59(12): 666-71, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20108654

RESUMO

4-Amino-N-(1-phenyl-1H-pyrazol-5-yl)-benzenesulfonamide (sulfaphenazole) 1 was selected as strategic starting material for the synthesis of some novel acetamide 2, pyrrole 4, pyrrolo[2,3-d]pyrimidine 5, thiocyanate 6, hydrazone 7a,b pyrazole 8, isothiocyanate 9 and thiophene 12 derivatives to evaluate theantitumor activity. Compound 4 was more effective than the reference drug, doxorubicin (CAS 23214-92-8) as positive control.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Pirazóis/síntese química , Pirazóis/farmacologia , Animais , Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Indicadores e Reagentes , Espectrometria de Massas , Espectrofotometria Infravermelho
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