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1.
J Enzyme Inhib Med Chem ; 34(1): 1388-1399, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392901

RESUMO

Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in µM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 µM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Dipeptídeos/química , Dipeptídeos/farmacologia , Sulfonamidas/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Antimaláricos/síntese química , Bactérias/efeitos dos fármacos , Dipeptídeos/síntese química , Fungos/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Testes de Sensibilidade Parasitária , Plasmodium falciparum/efeitos dos fármacos , Ratos , Sulfonamidas/química
2.
J Enzyme Inhib Med Chem ; 34(1): 1259-1270, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31287341

RESUMO

Pyrazolylphthalimide derivative 4 was synthesized and reacted with different reagents to afford the target compounds imidazopyrazoles 5-7, pyrazolopyrimidines 9, 12, 14 and pyrazolotriazines 16, 17 containing phthalimide moiety. The prepared compounds were established by different spectral data and elemental analyses. Additionally, all synthesized derivatives were screened for their antibacterial activity against four types of Gram + ve and Gram-ve strains, and for antifungal activity against two fungi micro-organisms by well diffusion method. Moreover, the antiproliferative activity was tested for all compounds against human liver (HepG-2) cell line in comparison with the reference vinblastine. Moreover, drug-likeness and toxicity risk parameters of the newly synthesized compounds were calculated using in silico studies. The data from structure-actvity relationship (SAR) analysis suggested that phthalimide derivative bearing 3-aminopyrazolone moiety, 4 illustrated the best antimicrobial and antitumor activities and might be considered as a lead for further optimization. To investigate the mechanism of the antimicrobial and anticancer activities, enzymatic assay and molecular docking studies were carried out on E. coli topoisomerase II DNA gyrase B and VEGFR-2 enzymes.


Assuntos
Ftalimidas/química , Ftalimidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Ftalimidas/síntese química , Análise Espectral/métodos , Relação Estrutura-Atividade
3.
J Photochem Photobiol B ; 197: 111556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326842

RESUMO

Facile green synthesis of copper nanoparticles from different biological procedures has been indicated, but among all, biosynthesis of copper nanoparticles from medicinal plants is considered as the most suitable method. The use of medicinal plant material increases the therapeutical effects of copper nanoparticles. The aim of this study was green synthesis of copper nanoparticles from aqueous extract of Falcaria vulgaris leaf (CuNPs) and assessment of their cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing properties. These nanoparticles were characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM) analysis. The synthesized CuNPs had great cell viability dose-dependently (Investigating the effect of the CuNPs on human umbilical vein endothelial cell (HUVEC) line) and indicated this method was nontoxic. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was done to assess the antioxidant activities, which indicated similar antioxidant potentials for CuNPs and butylated hydroxytoluene. In part of cutaneous wound healing property of CuNPs, after creating the cutaneous wound, the rats were randomly divided into six groups: treatment with 0.2% CuNPs ointment, treatment with 0.2% CuSO4 ointment, treatment with 0.2% F. vulgaris ointment, treatment with 3% tetracycline ointment, treatment with Eucerin basal ointment, and untreated control. These groups were treated for 10 days. Treatment with CuNPs ointment remarkably increased (p ≤ .01) the wound contracture, vessel, hexosamine, hydroxyl proline, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate and substantially reduced (p ≤ .01) the wound area, total cells, neutrophil, and lymphocyte compared to other groups. In antibacterial and antifungal parts of this research, the concentration of CuNPs with minimum dilution and no turbidity was considered minimum inhibitory concentration (MIC). To determine minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC), 60 µL MIC and three preceding chambers were cultured on Sabouraud Dextrose Agar and Muller Hinton Agar, respectively. The minimum concentration with no fungal and bacterial growth were considered MFC and MBC, respectively. CuNPs inhibited the growth of all fungi at 2-4 mg/mL concentrations and removed them at 4-8 mg/mL concentrations (p ≤ .01). In case of antibacterial effects of CuNPs, they inhibited the growth of all bacteria at 2-8 mg/mL concentrations and removed them at 4-16 mg/mL concentrations (p ≤ .01). The results of XRD, FT-IR, UV, TEM, and FE-SEM confirm that the aqueous extract of F. vulgaris leaf can be used to yield copper nanoparticles with notable amount of antioxidant, antifungal, antibacterial, and cutaneous wound healing potentials without any cytotoxicity. Further clinical trials are necessary for confirmation these therapeutical effects of CuNPs in human.


Assuntos
Apiaceae/química , Cobre/química , Nanopartículas Metálicas/química , Extratos Vegetais/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/química , Apiaceae/metabolismo , Candida/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Folhas de Planta/metabolismo , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Cicatrização/efeitos dos fármacos
4.
Future Microbiol ; 14: 587-598, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31148472

RESUMO

Aim: 17 new 4-methoxynaphthalene-N-acylhydrazones were synthesized in order to evaluate their biological action against important pathogens. Methods: In vitro susceptibility assays of compounds were performed against Paracoccidioides brasiliensis and Mycobacterium tuberculosis. Results: Compounds 4a, 4b and 4k were the most potent against P. brasiliensis, two with minimum inhibitory concentrations of ≤1 µg ml-1 and exhibited pharmacological synergy with amphotericin B. The compounds also showed activity against M. tuberculosis, with 4c and 4k being the more promising. Compound 4k showed good synergistic antimycobacterium activity with ethambutol. None of the compounds tested showed toxicity. Conclusion: We highlight the compound 4k, as a potential agent for the treatment of patients co-infected with paracoccidioidomycosis and tuberculosis.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Coinfecção/tratamento farmacológico , Mycobacterium tuberculosis/efeitos dos fármacos , Paracoccidioides/efeitos dos fármacos , Paracoccidioidomicose/tratamento farmacológico , Tuberculose/tratamento farmacológico , Anfotericina B/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Combinação de Medicamentos , Descoberta de Drogas , Sinergismo Farmacológico , Etambutol/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/patogenicidade , Paracoccidioides/patogenicidade
6.
Eur J Med Chem ; 177: 374-385, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31158751

RESUMO

To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of l-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03-0.06 µg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1-2 µg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent.


Assuntos
Amino Álcoois/farmacologia , Antifúngicos/farmacologia , Células A549 , Amino Álcoois/síntese química , Amino Álcoois/metabolismo , Amino Álcoois/toxicidade , Antifúngicos/síntese química , Antifúngicos/metabolismo , Antifúngicos/toxicidade , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/enzimologia , Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Domínio Catalítico , Cryptococcus neoformans/efeitos dos fármacos , Desenho de Drogas , Estabilidade de Medicamentos , Ergosterol/metabolismo , Humanos , Testes de Sensibilidade Microbiana , Ligação Proteica , Estereoisomerismo , Esterol 14-Desmetilase/química , Esterol 14-Desmetilase/metabolismo , Relação Estrutura-Atividade
7.
Eur J Med Chem ; 178: 515-529, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31207463

RESUMO

Carvacrol (CAR), a natural monoterpene particularly abundant in plants belonging to the Lamiaceae family, has recently attracted much attention for its many biological properties (antioxidant, anti-inflammatory, neuroprotective, antitumour, antibacterial, and several others). However, CAR has poor chemical-physical properties (low water solubility and high volatility), which hamper its potential pharmacological uses. In this paper, the synthesis and antimicrobial evaluation of 23 carvacrol derivatives (WSCP1-23) against a panel of selected gram-positive and gram-negative bacteria are reported. Using the prodrug approach, CAR hydrophilic (WSCP1-17) and lipophilic prodrugs (WSCP18-23) were prepared. Notably, CAR water solubility was increased by using polar neutral groups (such as natural amino acids) with the aim of improving oral drug delivery. On the other hand, CAR lipophilic prodrugs, obtained by prenylation of CAR hydroxyl group, were designed to promote membrane permeation and oral absorption. Our results revealed that WSCP1-3, showing the highest water solubility (>1700-fold compared to that of CAR), possessed good antibacterial activity against gram-negative bacteria with MIC values comparable to those of CAR and antifungal properties against different species of Candida. WSCP18-19 were the most promising prodrugs, showing good antibacterial profiles against gram-positive bacteria by interfering with the biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis. Moreover, WSCP18-19 resulted more stable in simulated fluids and human plasma than WSCP1-3. Toxicity studies performed on human erythrocytes and HaCaT cells revealed that all WSCPs were not toxic at the tested concentrations.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Monoterpenos/farmacologia , Pró-Fármacos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Candida/efeitos dos fármacos , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monoterpenos/síntese química , Monoterpenos/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Solubilidade , Relação Estrutura-Atividade
8.
Drug Discov Ther ; 13(2): 62-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080205

RESUMO

In the present study, silver nanoparticles (AgNPs) were synthesized by green synthesis using Psidium guajava aqueous extract (PE) as a reducing agent and silver nitrate (AgNO3) as a precursor. The obtained AgNPs showed maximum absorbance at 455 nm. The results from energy-dispersive X-ray spectroscopy demonstrate Ag signal at 88.33% weight. The particle image under scanning electron microscopy is spherical shape. The average size of the freshly prepared AgNPs is 96 ± 4 nm but is dramatically increases during storage due to particle aggregation. Coating AgNPs with polymeric micelles of poloxamer 407 (F127) at the suitable ratio can decrease the size of the freshly prepared AgNPs to 70.4 ± 0.8 nm and significantly prevent AgNPs from aggregation. The obtained coated AgNPs showed high effective on inhibition of Candida albicans. Isotonic solutions of 0.9% NaCl and phosphate buffer solution pH 7.4 can cause some extend of aggregation and increase the particle size of the coated AgNPs but the increased size is in the colloidal range that no precipitation occurs during 90 days at room temperature. From our results, it is suggested that the 1:1 ratio of AgNPs/F127 is the most suitable ratio to obtain the AgNPs loaded polymeric micelles with high stability, small particle size, and high inhibitory activity against C. albicans. These AgNPs are the promising antifungal nanomaterials for further study in animal model.


Assuntos
Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Extratos Vegetais/química , Psidium/química , Prata/química , Antifúngicos/química , Antifúngicos/farmacologia , Química Verde , Nanopartículas Metálicas/química , Micelas , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Poloxâmero/química , Espectrometria por Raios X
9.
Carbohydr Polym ; 216: 54-62, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047082

RESUMO

Biodegradable, antimicrobial, and semiconducting cellulosic composite was synthesized by in-situ polymerization of polyaniline in the presence of cellulose. The cobalt ferrite nanoparticles (CFO-NPs) were added during the polymerization process to acquire this composite magnetic property. The CFO-NPs were prepared by sol-gel method with average particles size less than 50 nm. The nanocomposites were characterized by Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX). In addition, their magnetic, dielectric constant, dielectric loss, and conductivity behaviors were studied. The magnetization (Ms) and conductivity increased up to 3.7 emu/g and 3.5 × 10-3 S/cm, respectively, with increasing CFO-NPs content. The prepared electromagnetic nanocomposite exhibits highly efficient biodegradability and antimicrobial activity against Escherichia coli, Bacillus subtilis, and Candida albicans. The antimicrobial activity increased with increasing CFO-NPs while the biodegradability decreased.


Assuntos
Compostos de Anilina/farmacologia , Celulose/farmacologia , Cobalto/farmacologia , Compostos Férricos/farmacologia , Nanocompostos/química , Nanopartículas/química , Compostos de Anilina/síntese química , Compostos de Anilina/química , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Plásticos Biodegradáveis/síntese química , Plásticos Biodegradáveis/química , Plásticos Biodegradáveis/farmacologia , Candida albicans/efeitos dos fármacos , Celulose/análogos & derivados , Celulose/síntese química , Cobalto/química , Condutividade Elétrica , Escherichia coli/efeitos dos fármacos , Compostos Férricos/síntese química , Compostos Férricos/química , Fenômenos Magnéticos , Tamanho da Partícula
10.
Molecules ; 24(9)2019 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-31060338

RESUMO

A new series of coumarin derivatives, 7-hydroxy-7-(trifluoromethyl)-6a,12b-dihydro-6H,7H-chromeno[3,4-c]chromen-6-ones 3a-p, were synthesized via Michael addition, transesterification and nucleophilic addition from the reaction of 3-trifluoroacetyl coumarins and phenols in the presence of an organic base. The products were characterized by infrared spectroscopy (IR), hydrogen nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR) and high-resolution mass spectrometer (HRMS). Single crystal X-ray analysis of compounds 3a and 3n clearly confirmed their assigned chemical structures and their twisted conformations. Compound 3a crystallized in the orthorhombic system, Pbca, in which a = 8.6244(2) Å, b = 17.4245(4) Å, c = 22.5188(6) Å, α = 90°, ß = 90°, γ = 90°, v = 3384.02(14) Å3, and z = 8. In addition, the mycelial growth rate method was used to examine the in vitro antifungal activities of the title compounds 3a-p against Fusarium graminearum and Fusarium monitiforme at 500 µg/mL. The results showed that compound 3l exhibited significant anti-Fusarium monitiforme activity with inhibitory index of 84.6%.


Assuntos
Antifúngicos/síntese química , Benzopiranos/síntese química , Cumarínicos/química , Fusarium/efeitos dos fármacos , Antifúngicos/química , Antifúngicos/farmacologia , Benzopiranos/química , Benzopiranos/farmacologia , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Estrutura Molecular , Espectroscopia de Prótons por Ressonância Magnética , Relação Estrutura-Atividade
11.
Eur J Med Chem ; 175: 201-214, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078867

RESUMO

Herein we report the design, synthesis, molecular docking study and evaluation of antimicrobial activity of ten new dithioloquinolinethiones. The structures of compounds were confirmed by 1H NMR, 13C NMR and HPLC-HRMS. Before evaluation of their possible antimicrobial activity prediction of toxicity was performed. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. All compounds appeared to be more active than ampicillin and almost all than streptomycin. The best antibacterial activity was observed for compound 8c 4,4,8-trimethyl-5-{[(4-phenyl-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)thio]acetyl}-4,5-dihydro-1H-[1,2]dithiolo[3,4c]quino lone-1-thione). The most sensitive bacterium En.cloacae followed by S. aureus, while L.monocytogenes was the most resistant. All compounds were tested for antifungal activity also against eight fungal species. The best activity was expressed by compound 8d (5-[(4,5-Dihydro-1,3-thiazol-2-ylthio)acetyl]-4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione). The most sensitive fungal was T. viride, while P. verrucosum var. cyclopium was the most resistant one. All compounds were more potent as antifungal agent than reference compound bifonazole and ketoconazole. The docking studies indicated a probable involvement of E. coli DNA GyrB inhibition in the anti-bacterial mechanism, while CYP51ca inhibition is probably responsible for antifungal activity of tested compounds. It is interesting to mention that docking results coincides with experimental.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Cromatografia Líquida de Alta Pressão , Desenho de Drogas , Fungos/classificação , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Espectroscopia de Prótons por Ressonância Magnética , Quinolinas/síntese química , Relação Estrutura-Atividade
12.
Chem Biodivers ; 16(7): e1900118, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31106521

RESUMO

In continuation of our previous research on the development of novel pyrazole-4-carboxamide with potential antifungal activity, compound SCU2028, namely N-[2-[(3-chlorophenyl)amino]phenyl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, was synthesized by new method, structurally characterized by IR, HR-ESI-MS, 1 H- and 13 C-NMR spectra and further identified by single-crystal X-ray diffraction. In pot tests, compound SCU2028 showed good in vivo antifungal activity against Rhizoctonia solani (R. solani) and IC50 value of it was 7.48 mg L-1 . In field trials, control efficacy of compound SCU2028 at 200 g.a.i. ha-1 was 42.30 % on the 7th day after the first spraying and 68.10 % on the 14th day after the second spraying, only slightly lower than that of thifluzamide (57.20 % and 71.40 %, respectively). Further in vitro inhibitory activity showed inhibitory ability of compound SCU2028 was 45-fold higher than that of bixafen and molecular docking of compound SCU2028 to SDH predicted its binding orientation in the active site of the target protein SDH. These results suggested that compound SCU2028 was a potential fungicide for control of rice sheath blight.


Assuntos
Antifúngicos/farmacologia , Simulação de Acoplamento Molecular , Pirazóis/farmacologia , Rhizoctonia/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Cristalografia por Raios X , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química
13.
Curr Top Med Chem ; 19(13): 1145-1161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31119999

RESUMO

BACKGROUND: Griseofulvin - a mold metabolite produced by Penisilium griseofulvum is known as an antifungal drug. OBJECTIVE: Thus, the goal of this paper is the design and synthesis of new griseofulvin derivatives and evaluation of their antifungal activity. METHODS: Forty-two new compounds were synthesized using classical methods of organic synthesis and evaluated for their antimicrobial activity by microdilution method. RESULTS: All forty-two new compounds exhibited very good activity against eight tested micromycetes with MIC ranging from 0.0075-0.055 mg/ml and MFC from 0.02-024 mg/ml. All compounds exhibited better activity than reference drugs ketoconazole (7-42 times) and bifonazole (3-16 fold). The most promising was compound 15. The most sensitive fungal was found to be T. viride, while the most resistant, as was expected, was A. fumigatus. It should be mentioned that most of compounds exhibited better activity than griseofulvin. The molecular docking studies revealed that the most active compound have the same hydrophobic and H-bonding interactions with Thr276 residue observed for griseofulvin forming 3 hydrogen bonds while griseofulvin only one. In general, the molecular docking results coincide with experimental. CONCLUSION: Forty-two giseofulvin derivatives were designed, synthesized and evaluated for antimicrobial activity. These derivatives revealed good antifungal activity, better than reference drugs ketoconazole, bifonazole, and griseofulvin as well.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Griseofulvina/farmacologia , Simulação de Acoplamento Molecular , Trichoderma/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Relação Dose-Resposta a Droga , Griseofulvina/síntese química , Griseofulvina/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
14.
Eur J Med Chem ; 173: 228-239, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009909

RESUMO

In continuation of our program to discover new potential antifungal agents, thirty-two neuchromenin analogues were synthesized and characterized by the spectroscopic analysis. By using the mycelium growth rate method, the target compounds were evaluated systematically for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Compounds 6b-c, and 6l showed obvious inhibition activity on each of the fungi at 50 µg/mL. For the corresponding fungi, 7 of the compounds showed average inhibition rates of >80% at 50 µg/mL; especially, compounds 6b, 6d-e, and 6i-l displayed more potent antifungal activity against A. solani than that of thiabendazole (a positive control). Moreover, compound 6c also exhibited good activity against C. lunata with EC50 values of 12.7 µg/mL, and the value was much superior to that of thiabendazole (EC50 = 59.7 µg/mL). SAR analysis showed that the presence of conjugated structure, bearing a C=C bond conjugated to the C=O group, obviously decreased the activity; the type and position of the substituted R5 significantly influenced the activity. Furthermore, the significantly bioactive compounds 6b-e, 6g, 6i and 6l showed very low toxicities against HL-7702, BEL-7402 and HCT-8 cells. Resistance development assay indicated that compounds 6b-e and 6l failed to induce the two tested strains of fungi to develop resistance. SEM analysis initially revealed that compound 6d may exert its antifungal effect by damaging fungal cell wall.


Assuntos
Antifúngicos/farmacologia , Desenho de Drogas , Fungos/efeitos dos fármacos , Antifúngicos/síntese química , Antifúngicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
15.
Eur J Med Chem ; 173: 250-260, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31009911

RESUMO

Fungal cell surface carbohydrates and proteins are useful antigens for the development of antifungal vaccines. In this study, glycopeptides consisting of the ß-1,2-mannan and N-terminal peptide epitopes of Candida albicans (C. albicans) cell wall phosphomannan complex and Als1p (rAls1p-N) protein, respectively, were synthesized and covalently conjugated with keyhole limpet hemocyanin (KLH) and human serum albumin (HSA) through homobifunctional disuccinimidyl glutarate. The resultant KLH-conjugates were immunologically evaluated using Balb/c mice to reveal that they induced high levels of IgG antibodies. Furthermore, these conjugates showed self-adjuvanting property, as they could promote robust antibody responses without the presence of an external adjuvant. More significantly, the obtained antisera could effectively recognize both the carbohydrate and the Als1 peptide epitopes and immunofluorescence and flow cytometry assays also demonstrated that the elicited antibodies could react with the cell surface of a number of fungi, including C. albicans, C. tropicalis, C. lustaniae and C. glabrata. These results suggested the great potential of these conjugates as antifungal vaccines.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Mananas/farmacologia , Peptídeos/farmacologia , Vacinas/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Candida/citologia , Relação Dose-Resposta a Droga , Mananas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptídeos/química , Relação Estrutura-Atividade , Vacinas/síntese química , Vacinas/química
16.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987115

RESUMO

A series of novel 3-aryl-4-hydroxy-2(5H) furanone-acrylate hybrids were designed and synthesized based on the natural butenolides and acrylates scaffolds. The structures of the prepared compounds were characterized by ¹H-NMR, 13C-NMR and electrospray ionization mass spectrometry (ESI-MS), and the bioactivity of the target compounds against twelve phytopathogenic fungi was investigated. The preliminary in vitro antifungal activity screening showed that most of the target compounds had moderate inhibition on various pathogenic fungi at the concentration of 100 mg·L-1, and presented broad-spectrum antifungal activities. Further studies also indicated that compounds 7e and 7k still showed some inhibitory activity against Pestallozzia theae, Sclerotinia sclerotiorum and Gibberella zeae on rape plants at lower concentrations, which could be optimized as a secondary lead for further research.


Assuntos
4-Butirolactona/análogos & derivados , Acrilatos/síntese química , Acrilatos/farmacologia , 4-Butirolactona/síntese química , 4-Butirolactona/química , 4-Butirolactona/farmacologia , Acrilatos/química , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Produtos Biológicos/síntese química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Estrutura Molecular , Relação Estrutura-Atividade
17.
Mater Sci Eng C Mater Biol Appl ; 101: 323-329, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029325

RESUMO

In this study, the antifungal activity rate of alginate-CuO bionanocomposite was assessed against Aspergillus niger using colony forming units (CFU) and disc diffusion methods. Employing the Taguchi method, nine experiments were designed for the synthesis of alginate-CuO nanocomposite with the highest antifungal activity. The nanocomposite synthesized under the conditions of experiment 5 (4 mg/mL CuO nanoparticles and 1 mg/mL alginate biopolymer with stirring time of 90 min) showed the greatest inhibition rate on fungal growth (83.17%). In the optimum conditions for the synthesis of alginate-CuO nanocomposite with the highest antifungal activity the second level of CuO NPs (14.14%), alginate biopolymer (8.16%) and stirring time (5.63%) showed the best improvement performance on inhibiting the fungal growth. The results of ultraviolet-visible spectroscopy (UV-vis), transmission electron microscopy (TEM) and X-ray powder diffraction (XRD) confirmed the formation of alginate-CuO nanocomposite. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) indicated that the thermal stability of alginate biopolymer and CuO nanoparticles were improved by the formation of the nanocomposite. Due to the favorable properties of alginate-CuO nanocomposite, its antifungal feature can be used in various biomedical fields.


Assuntos
Alginatos/síntese química , Alginatos/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Materiais Biocompatíveis/síntese química , Cobre/farmacologia , Nanocompostos/química , Temperatura Ambiente , Alginatos/química , Antifúngicos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/crescimento & desenvolvimento , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Cobre/química , Testes de Sensibilidade Microbiana , Nanocompostos/ultraestrutura , Espectrofotometria Ultravioleta , Termogravimetria , Difração de Raios X
18.
Carbohydr Polym ; 215: 108-118, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981335

RESUMO

In the current study, five novel urea-functionalized chitosan derivatives were synthesized via condensation reactions of chloroacetyl chitosan (CTCS) with urea groups bearing nitrogen-containing heterocycles. In order to identify the structure characteristics of chitosan derivatives, FT-IR, 1H NMR spectroscopy, and elemental analysis were carried out. The antifungal activity of the derivatives against four species of phytopathogen (Fusarium oxysporum f. sp. niveum, Phomopsis asparagus, Fusarium oxysporum f. sp. cucumebrium Owen, and Botrytis cinerea) was evaluated. Furthermore, the antioxidant activity of chitosan derivatives was tested by hydroxyl-radical scavenging and superoxide-radical scavenging assays. The results indicated that chitosan derivatives bearing urea groups displayed superior bioactivity compared with chitosan. Besides, L929 cells were adopted for cytotoxicity test of chitosan and synthesized samples by CCK-8 assay and all samples showed decreased cytotoxicity. These results suggested that the novel urea-functionalized chitosan derivatives could be an ideal biomaterial for antifungal and antioxidant applications.


Assuntos
Antifúngicos , Antioxidantes , Quitosana , Animais , Antifúngicos/síntese química , Antifúngicos/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Camundongos , Ureia/química
19.
Molecules ; 24(6)2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30871137

RESUMO

The quaternization reactions of nicotinamide, with different electrophiles: methyl iodide and substituted 2-bromoacetophenones (4-Cl, 4-Br, 4-H, 4-CH3, 4-F, 4-OCH3, 4-Ph, 2-OCH3, 4-NO2) are reported. The preparations were carried out by conventional synthesis and under microwave irradiation in absolute ethanol and acetone. The synthesis performed by microwave dielectric heating significantly improved yield, up to 8 times, and shortened down the reaction time from ca. one day in conventional, to 10⁻20 min. The structures of the synthesized compounds were confirmed by IR, ¹H- and 13C-NMR spectroscopy, mass spectrometry and elemental analysis. The compounds have been screened for antifungal activities against Fusarium oxysporum, Fusarium culmorum, Macrophomina phaseolina and Sclerotinia sclerotiorum at concentrations of 10 µg/mL and 100 µg/mL. Six compounds showed the strong inhibition of mycelium growth at a concentration of 10 µg/mL. All tested compounds revealed the great inhibitory activities against S. sclerotiorum at a concentration of 100 µg/mL.


Assuntos
Antifúngicos/síntese química , Ascomicetos/efeitos dos fármacos , Fusarium/efeitos dos fármacos , Niacinamida/análogos & derivados , Piridinas/síntese química , Acetofenonas/química , Antifúngicos/química , Antifúngicos/farmacologia , Hidrocarbonetos Iodados/química , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Micro-Ondas , Estrutura Molecular , Niacinamida/química , Piridinas/química , Piridinas/farmacologia
20.
Molecules ; 24(5)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30866442

RESUMO

Sporotrichosis is a neglected fungal infection caused by Sporothrix spp., which have a worldwide distribution. The standard antifungal itraconazole has been recommended as a first-line therapy. However, failure cases in human and feline treatment have been reported in recent years. This study aimed to synthesize several α- and ß-2,3-dihydrofuranaphthoquinones and evaluate them against Sporothrix schenckii and Sporothrix brasiliensis-the main etiological agents of sporotrichosis in Brazil. The stability of these compounds was also investigated under different storage conditions for 3 months. The samples were removed at 0, 60, and 90 days and assessed by ¹H-NMR, and their in vitro antifungal susceptibility was tested. Furthermore, we evaluated the superficial changes caused by the most effective and stable compounds using scanning electron microscopy and determined their effects when combined with itraconazole. Nine dihydrofuranaphthoquinones showed good antifungal activity and stability, with MIC values of 2⁻32 µM. Compounds 6 and 10 were the most active dihydrofuranaphthoquinones in vitro for both species; in fungi, these compounds induced yeast⁻hyphae conversion and alteration in the hyphae and conidia structures. Compound 10 also exhibited a synergistic activity with itraconazole against S. schenckii, with a ΣFIC index value of 0.3. Our results indicate that Compounds 6 and 10 are potential candidates for the development of new antifungal agents for the treatment of sporotrichosis.


Assuntos
Antifúngicos/síntese química , Furanos/síntese química , Itraconazol/farmacologia , Naftoquinonas/síntese química , Sporothrix/efeitos dos fármacos , Antifúngicos/química , Antifúngicos/farmacologia , Brasil , Estabilidade de Medicamentos , Sinergismo Farmacológico , Furanos/química , Furanos/farmacologia , Humanos , Hifas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/farmacologia , Esporos Fúngicos/efeitos dos fármacos
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