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1.
Biomed Pharmacother ; 133: 111052, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378958

RESUMO

The irrational use of medications has increased the incidence of microbial infections, which are a major threat to public health. Moreover, conventional therapeutic strategies are starting to become ineffective to treat these infections. Hence, there is a need to develop and characterize novel antimicrobial compounds. Phytochemicals are emerging as a safe and accessible alternative to conventional therapeutics for treating infectious diseases. Curcumin is extracted from the dried rhizome of the spice turmeric (Curcuma longa (Zingiberaceae)). However, the bioavailability of curcumin is low owing to its lipophilic property and thus has a low therapeutic efficacy in the host. A previous study synthesized structural variants of curcumin, which are called monocurcuminoids (CNs). CNs are synthesized based on the chemical structure of curcumin with only one methyl bridge. The biological activities of four previously synthesized CNs (CN59, CN63, CN67, and CN77), curcumin, and turmeric powder were examined in this study. Gas chromatography-tandem mass spectrometry analysis of curcumin and turmeric powder revealed similar peaks, which indicated the presence of curcumin in turmeric powder. The antioxidant activity of the test compounds was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assays. The ABTS radical scavenging activities of the test compounds were similar to those of vitamin C. The minimum inhibitory concentration (MIC) values of the test compounds against seven microbial strains were in the range of 4.06-150 µg/mL. The MIC value was equal to minimum bactericidal concentration value for CN63 (150 µg/mL) and CN67 (120 µg/mL) against Staphylococcus aureus. The treatment combination of CN77 (8.75 or 4.37 µg/mL) and turmeric powder (9.37 or 4.68 µg/mL) exerted synergistic growth-inhibiting effects on Aeromonas hydrophila, Candida albicans, and Pseudomonas aeruginosa. Photodynamic therapy using 2X MIC of CN59 decreased the growth of Enterococcus faecalis by 4.18-fold compared to the control group and completely inhibited the growth of Escherichia coli. The results of the hemolytic assay revealed that the test compounds were not cytotoxic with half-maximal inhibitory concentration values ranging from 49.65-130.9 µM. The anticoagulant activity of most compounds was comparable to that of warfarin but higher than that of heparin. This indicated that these compounds target the intrinsic coagulation pathway. These results demonstrated that these CNs are a safe and promising alternative for curcumin.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Bactérias/efeitos dos fármacos , Bioprospecção , Candida albicans/efeitos dos fármacos , Diarileptanoides/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/toxicidade , Antioxidantes/síntese química , Antioxidantes/toxicidade , Bactérias/crescimento & desenvolvimento , Benzotiazóis/química , Compostos de Bifenilo/química , Coagulação Sanguínea/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Diarileptanoides/síntese química , Diarileptanoides/toxicidade , Resistência Microbiana a Medicamentos , Hemólise/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/toxicidade , Picratos/química , Carneiro Doméstico , Ácidos Sulfônicos/química
2.
Int J Nanomedicine ; 15: 5951-5961, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848398

RESUMO

During the last decade green synthesized cerium oxide nanoparticles (CeO2 NPs) attracted remarkable interest in various fields of science and technology. This review, explores the vast array of biological resources such as plants, microbes, and other biological products being used in synthesis of CeO2 NPs. It also discusses their biosynthetic mechanism, current understandings, and trends in the green synthesis of CeO2 NPs. Novel therapies based on green synthesized CeO2 NPs are illustrated, in particular their antimicrobial potential along with attempts of their mechanistic elucidation. Overall, the main objective of this review is to provide a rational insight of the major accomplishments of CeO2 NPs as novel therapeutics agents for a wide range of microbial pathogens and combating other diseases.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Cério/química , Nanopartículas Metálicas/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Química Verde , Extratos Vegetais/química
3.
J Med Chem ; 63(11): 5797-5815, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32400157

RESUMO

Because of the rapid increase in bacterial resistance, there is an urgent need for developing new antimicrobial agents to combat multidrug-resistant pathogens. In this study, we designed and synthesized a series of kaempferol derivatives as antimicrobial agents biomimicking the structural properties and biological functions of host defense peptides. After fine-tuning of hydrophobic and cationic hydrophilic moieties linked to the flavone scaffold of kaempferol, we obtained a lead compound (52) that displayed high membrane selectivity (>128), poor hemolytic activity, low cytotoxicity to mammalian cells, and excellent activity against Gram-positive bacteria (minimum inhibitory concentrations = 1.56 µg/mL), including methicillin-resistant Staphylococcus aureus. Compound 52 can kill bacteria quickly by destroying the bacterial membranes and avoid developing bacterial resistance. Moreover, compound 52 exhibited potent in vivo antibacterial activity against S. aureus in a murine corneal infection model. These results indicated that compound 52 had the therapeutic potential as a novel membrane-active antimicrobial to combat Gram-positive bacterial infections.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias Gram-Positivas/efeitos dos fármacos , Quempferóis/química , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doenças da Córnea/tratamento farmacológico , Doenças da Córnea/microbiologia , Modelos Animais de Doenças , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Hemólise/efeitos dos fármacos , Humanos , Quempferóis/farmacologia , Quempferóis/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade
4.
Biochim Biophys Acta Biomembr ; 1862(9): 183353, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407778

RESUMO

Semisynthetic γ-mangostin derivative LS02 is a novel cationic amphiphilic peptidomimetic antimicrobial agent containing a hydrophobic scaffold and three hydrophilic and positively charged residues of arginine. LS02 showed low in vitro toxicity, potent activities against Gram-positive bacteria including MRSA (MIC = 1.56-6.25 µg/mL) and avoidance of drug resistance. The mode of action studies indicated that LS02 killed bacteria by disrupting bacterial cell membranes. LS02 not only exhibited good water solubility, low hemolytic activity and cell cytotoxicity, but also displayed excellent in vitro and in vivo antibacterial activity, indicating its great potential of being a lead compound as a novel membrane-active antibacterial agent capable of combating bacterial resistance.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Peptidomiméticos , Xantonas , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Feminino , Humanos , Células MCF-7 , Camundongos , Peptidomiméticos/síntese química , Peptidomiméticos/química , Peptidomiméticos/farmacologia , Coelhos , Xantonas/síntese química , Xantonas/química , Xantonas/farmacologia
5.
Molecules ; 25(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32012912

RESUMO

: The synthesis of metal nanoparticles using plant extracts is a very promising method in green synthesis. The medicinal value of Moringa oleifera leaves and the antimicrobial activity of metallic copper were combined in the present study to synthesize copper nanoparticles having a desirable added-value inorganic material. The use of a hydroalcoholic extract of M. oleifera leaves for the green synthesis of copper nanoparticles is an attractive method as it leads to the production of harmless chemicals and reduces waste. The total phenolic content in the M. oleifera leaves extract was 23.0 ± 0.3 mg gallic acid equivalent/g of dried M. oleifera leaves powder. The M. oleifera leaves extract was treated with a copper sulphate solution. A color change from brown to black indicates the formation of copper nanoparticles. Characterization of the synthesized copper nanoparticles was performed using ultraviolet-visible light (UV-Vis) spectrophotometry, Fourier-transform infrared (FTIR) spectrometry, high-resolution transmission electron microscopy (HRTEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized copper nanoparticles have an amorphous nature and particle size of 35.8-49.2 nm. We demonstrate that the M. oleifera leaves extract and the synthesized copper nanoparticles display considerable antioxidant activity. Moreover, the M. oleifera leaves extract and the synthesized copper nanoparticles exert considerable anti-bacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis (MIC values for the extract: 500, 250, 250, and 250 µg/mL; MIC values for the copper nanoparticles: 500, 500, 500, and 250 µg/mL, respectively). Similarly, the M. oleifera leaves extract and the synthesized copper nanoparticles exert relatively stronger anti-fungal activity against Aspergillus niger, Aspergillus flavus, Candida albicans, and Candida glabrata (MIC values for the extract: 62.5, 62.5, 125, and 250 µg/mL; MIC values for the copper nanoparticles: 125, 125, 62.5, and 31.2 µg/mL, respectively). Our study reveals that the green synthesis of copper nanoparticles using a hydroalcoholic extract of M. oleifera leaves was successful. In addition, the synthesized copper nanoparticles can be potentially employed in the treatment of various microbial infections due to their reported antioxidant, anti-bacterial, and anti-fungal activities.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Cobre/química , Moringa oleifera/química , Fenóis/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antioxidantes/síntese química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Cápsulas , Fungos/efeitos dos fármacos , Química Verde , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Extratos Vegetais/química , Folhas de Planta/química
6.
Molecules ; 25(4)2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32059480

RESUMO

Bacterial resistance remains a significant threat and a leading cause of death worldwide, despite massive attempts to control infections. In an effort to develop biologically active antibacterial and antifungal agents, six novel aryl-substituted-1,2,3-triazoles linked to carbohydrate units were synthesized through the Cu(I)-catalyzed azide-alkyne cycloaddition CuAAC of substituted-arylazides with a selection of alkyne-functionalized sugars. The chemical structures of the new derivatives were verified using different spectroscopic techniques. The novel clicked 1,2,3-triazoles were evaluated for in vitro antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, and the obtained results were compared with the activity of the reference antibiotic "Ampicillin". Likewise, in vitro antifungal activity of the new 1,2,3-triazoles was investigated against Candida albicans and Aspergillus niger using "Nystatin" as a reference drug. The results of the biological evaluation pointed out that Staphylococcus aureus was more susceptible to all of the tested compounds than other examined microbes. In addition, some tested compounds exhibited promising antifungal activity.


Assuntos
Anti-Infecciosos/farmacologia , Química Click , Glicosídeos/farmacologia , Triazóis/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/patogenicidade , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Glicosídeos/síntese química , Glicosídeos/química , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Relação Estrutura-Atividade , Triazóis/síntese química , Triazóis/química
7.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936505

RESUMO

In this paper, we aimed to exploit and combine in the same molecule the carbazole and the 1,3,4-oxadiazole pharmacophores, to obtain novel carprofen derivatives, by using two synthesis pathways. For the first route, the following steps have been followed: (i) (RS)-2-(6-chloro-9H-carbazol-2-yl)propanonic acid (carprofen) treatment with methanol, yielding methyl (RS)-2-(6-chloro-9H-carbazol-2-yl)propanoate; (ii) the resulted methylic ester was converted to (RS)-2-(6-chloro-9H-carbazol-2-yl)propane hydrazide (carprofen hydrazide) by treatment with hydrazine hydrate; (iii) reaction of the hydrazide derivative with acyl chlorides led to N-[(2RS)-2-(6-chloro-9H-carbazol-2-yl)propanoil]-N'-R-substituted-benzoylhydrazine formation, which; (iv) in reaction with phosphorus oxychloride gave the (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-(1,3,4-oxadiazol-2-yl)ethane derivatives. In the second synthesis pathway, new 1,3,4-oxadiazole ring compounds were obtained starting from carprofen which was reacted with isoniazid, in the presence of phosphorus oxychloride to form (RS)-1-(6-chloro-9H-carbazol-2-yl)-1-[5-(4-pyridyl)-1,3,4-oxadiazol-2-yl]ethane. The synthesized compounds were characterized by IR, 1H-NMR and 13C-NMR, screened for their drug-like properties and evaluated for in vitro cytotoxicity and antimicrobial activity. The obtained compounds exhibited a good antimicrobial activity, some of the compounds being particularly active on E. coli, while others on C. albicans. The most significant result is represented by their exceptional anti-biofilm activity, particularly against the P. aeruginosa biofilm. The cytotoxicity assay revealed that at concentrations lower than 100 µg/mL, the tested compounds do not induce cytotoxicity and do not alter the mammalian cell cycle. The new synthesized compounds show good drug-like properties. The ADME-Tox profiles indicate a good oral absorption and average permeability through the blood brain barrier. However, further research is needed to reduce the predicted mutagenic potential and the hepatotoxicity.


Assuntos
Antibacterianos/química , Anti-Infecciosos/química , Carbazóis/química , Oxidiazóis/química , Antibacterianos/síntese química , Antibacterianos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Carbazóis/síntese química , Carbazóis/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Oxidiazóis/síntese química , Oxidiazóis/farmacologia , Relação Estrutura-Atividade
8.
Int J Mol Sci ; 21(2)2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31941068

RESUMO

As a natural polysaccharide, chitosan possesses good biocompatibility, biodegradability and biosafety. Its hydroxyl and amino groups make it an ideal carrier material in the construction of polymer-drug conjugates. In recent years, various synthetic strategies have been used to couple chitosan with active substances to obtain conjugates with diverse structures and unique functions. In particular, chitosan conjugates with antimicrobial activity have shown great application prospects in the fields of medicine, food, and agriculture in recent years. Hence, we will place substantial emphasis on the synthetic approaches for preparing chitosan conjugates and their antimicrobial applications, which are not well summarized. Meanwhile, the challenges, limitations, and prospects of antimicrobial chitosan conjugates are described and discussed.


Assuntos
Anti-Infecciosos , Quitosana , Glicoconjugados , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Quitosana/química , Quitosana/uso terapêutico , Glicoconjugados/síntese química , Glicoconjugados/química , Glicoconjugados/uso terapêutico , Humanos
9.
Mater Sci Eng C Mater Biol Appl ; 108: 110339, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923981

RESUMO

In this study a novel and smart multi-functional hydrogel (MFH) was synthesized from N, N dimethyl acrylamide (DMAAm), gelatin, citric acid (CA) and pomegranate extract (PE) for instant and easy monitoring of the color change in MFH due to changes in medium conditions such as pH and temperature. MFH was utilized as food packaging material, equipped with the developed properties. MFH was synthesized with a redox polymerization technique in film form on petri dishes. Mechanical and water resistance properties of MFH were improved by CA and N, N, methylenebisacrylamide, while PE was used to gain antimicrobial, antioxidant and anthocyanin properties. Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analyzer (TGA), Liquid Chromatography-Mass Spectroscopy (LC-MS/MS) and Scanning Electron Microscopy (SEM) instruments were utilized for characterization of MFH. FTIR revealed the existence of bonding interactions between the functional group of PE and gelatin, carbonyl groups of DMAAm and carboxylic acid groups of CA. TGA results indicate that MFH was stable up to 400 °C. Then the response of total antioxidant and anthocyanin activities leading to the color change in MFH were studied at different pH values. The color change in MFH was monitored even at very small pH changes in the medium. Moreover, antimicrobial activity and stability of MFH were investigated when it was tested in harsh environments and against Escherichia coli, Bacillus subtilis and Staphylococcus aureus on real samples of whole pasteurized milk and cheese for a 7-day period. It exhibited remarkable antimicrobial activity with pasteurized whole milk and cheese. It was concluded that MFH is a very good candidate to be used as biodegradable food packaging material.


Assuntos
Acrilamidas/química , Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Embalagem de Alimentos , Gelatina/química , Extratos Vegetais/química , Romã (Fruta)/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia
10.
J Photochem Photobiol B ; 204: 111803, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32000112

RESUMO

Infectious diseases constitute a serious problem for human health and life. Although many bacterial and fungal infections can be successfully cured by commonly used antibiotics, a new threat emerges in the form of microbial resistance. For this reason, researchers try to find not only new active pharmaceutical ingredients for conventional antibiotherapy but also try to develop new strategies of microbial inactivation. Photodynamic antimicrobial chemotherapy, which relies on reactive oxygen species generated in situ in the presence of a photosensitizer and with the light of an appropriate wavelength, is one of them. Porphyrazines have been considered as potential photosensitizers for anticancer and antimicrobial photodynamic therapy. In this study, three tribenzoporphyrazines with dendrimeric peripheral substituents were subjected to in vitro antimicrobial photocytotoxicity study. One magnesium(II) tribenzoporphyrazine with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl substituents was synthesized and subjected to physicochemical characterization using NMR, UV-Vis, and mass spectrometry techniques. In photochemical studies this molecule revealed moderate singlet oxygen generation ability (ΦΔDMF = 0.12, ΦΔDMSO = 0.13). The other two magnesium(II) tribenzoporphyrazines applied in the biological study were 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl-substituted tribenzoporphyrazine and 4-[3,5-bis(benzyloxy)benzyloxy]phenyl-substituted tribenzopyrazinoporphyrazine. For the assessment, three microbial strains were chosen: Gram-positive bacteria Staphylococcus aureus ATCC 25923, Gram-negative bacteria Escherichia coli ATCC 25922, and fungal strain Candida albicans ATCC 10231. Very high activity against Staphylococcus aureus at low 10-6 M concentration was recorded for magnesium(II) tribenzoporphyrazines with peripheral 3,5-bis(3,5-dimethoxybenzyloxy)benzylsulfanyl and 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents with calculated log reductions of 4.4 and 4.8, respectively. It is worth noting that magnesium(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylsulfanyl substituents revealed also 3.2 log reduction in bacterial growth at the concentration 10-7 M.


Assuntos
Anti-Infecciosos/farmacologia , Dendrímeros/química , Pirazinas/química , Staphylococcus aureus/efeitos dos fármacos , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Candida albicans/efeitos dos fármacos , Candida albicans/efeitos da radiação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos da radiação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos da radiação , Luz , Testes de Sensibilidade Microbiana , Pirazinas/síntese química , Pirazinas/farmacologia , Oxigênio Singlete/metabolismo , Staphylococcus aureus/efeitos da radiação
11.
Folia Microbiol (Praha) ; 65(2): 393-405, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31401762

RESUMO

Nosocomial infections are an important cause of morbi-mortality worldwide. The increase in the rate of resistance to conventional drugs in these microorganisms has stimulated the search for new therapeutic options. The nitro moiety (NO2) is an important pharmacophore of molecules with high anti-infective activity. We aimed to synthesize new nitro-derivates and to evaluate their antibacterial and anti-Candida potential in vitro. Five compounds [3-nitro-2-phenylchroman-4-ol (3); 3-nitro-2-phenyl-2H-chromene (4a); 3-nitro-2-(4-chlorophenyl)-2H-chromene (4b); 3-nitro-2-(4-fluorophenyl)-2H-chromene (4c), and 3-Nitro-2-(2,3-dichlorophenyl)-2H-chromene (4d)] were efficiently synthesized by Michael-aldol reaction of 2-hydroxybenzaldehyde with nitrostyrene, resulting in one ß-nitro-alcohol (3) and four nitro-olefins (4a-4d). The antibacterial and anti-Candida potentials were evaluated by assaying minimal inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC). Mono-halogenated nitro-compounds (4b and 4c) showed anti-staphylococcal activity with MIC values of 15.6-62.5 µg/mL and MBC of 62.5 µg/mL. However, the activity against Gram-negative strains was showed to be considerably lower and our data suggests that this effect was associated with the outer membrane. Furthermore, nitro-compounds 4c and 4d presented activity against Candida spp. with MIC values ranging from 7.8-31.25 µg/mL and MFC of 15.6-500 µg/mL. In addition, these compounds were able to induce damage in fungal cells increasing the release of intracellular material, which was associated with actions on the cell wall independent of quantitative changes in chitin and ß-glucan. Together, these findings show that nitro-compounds can be exploited as anti-staphylococcal and anti-Candida prototypes.


Assuntos
Anti-Infecciosos/farmacologia , Nitrocompostos/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Desenho de Fármacos , Humanos , Testes de Sensibilidade Microbiana , Nitrocompostos/síntese química , Nitrocompostos/química
12.
Artigo em Inglês | MEDLINE | ID: mdl-30827265

RESUMO

BACKGROUND: Hydroxytriazenes and their derivatives have been studied for the biological and pharmacological applications in the past few years. These compounds possess antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities. In this study, we report the synthesis of ten hydroxytriazenes in two series derived from disubstituted aniline and studied for antimicrobial and anti-inflammatory activities. METHODS: For this purpose, 2-methyl-5-chloroaniline and 2-trifluoromethyl-5-chloroaniline were used to synthesize compounds A1-5 and B1-5 series, respectively. All compounds were synthesized by the reported method which involves three steps of the method (i) Reduction, (ii) Diazotization, (iii) Coupling. All synthesized compounds were characterized by various techniques CHN elemental analysis, FTIR, 1H NMR, and MASS spectral analysis. The antibacterial activities of the compounds were screened against S. aureus, S. pyogenes, E. coli, P. aeruginosa, and antifungal activities were against C. albicans, A. clavatus by the zone of inhibition method. In addition, anti-inflammatory activity was also evaluated by carrageenan-induced paw edema method and results were reported as % inhibition. RESULTS: All the synthesized compounds were obtained in pure form and their spectral data are in good agreement with their structure. The synthesized compounds have shown good antimicrobial activity and zone of inhibition was ranging 21 to 24 mm. Further antiinflammatory effect of the compounds was 96.58 to 98.71 % inhibition. CONCLUSION: The results of the present study indicate that chloro and trifluoromethyl substitution at hydroxytriazenes skeleton could improve anti-inflammatory and antimicrobial activities.


Assuntos
Anti-Infecciosos , Anti-Inflamatórios não Esteroides , Triazinas , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/crescimento & desenvolvimento , Triazinas/síntese química , Triazinas/farmacologia , Triazinas/uso terapêutico
13.
Mini Rev Med Chem ; 20(5): 418-429, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31161988

RESUMO

BACKGROUND & OBJECTIVE: Quinazolines and their fused systems are noteworthy in pharmaceutical chemistry due to their wide range of biological activities. METHODS: A direct and efficient approach for the synthesis of new series of fused quinazolines with triazole, thiazole, benzimidazole and tetrazole has been preceded via the reaction of quinazoline thione derivative with halogenated compounds or cyclocondensation of arylidene of quinazoline derivative with heterocyclic amines. Also, dibenzo[b,e][1,4]thiazepine derivatives was synthesized through the reaction of 2,6-bis-(2-chloro-benzylidene)-cyclohexanone with o-aminothiophenol. RESULTS: The structures of all new synthesized heterocyclic compounds were confirmed and discussed on the bases of spectral data. The utility of the preparation and design of the above mentioned compounds has been shown to be clear in the results of their antimicrobial activity which revealed that some derivatives have potent activity exceeding or similar to the activity of the reference drugs. CONCLUSION: The insertion of triazole or thiazole moieties to be fused with quinazoline ring helps to enhance its antimicrobial activity.


Assuntos
Quinazolinas/química , Quinazolinas/síntese química , Quinazolinas/farmacologia , Tiazepinas/química , Tiazepinas/síntese química , Tiazepinas/farmacologia , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Azóis/síntese química , Azóis/química , Azóis/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade
14.
Biochim Biophys Acta Biomembr ; 1862(2): 183092, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31678367

RESUMO

Antimicrobial peptides (AMPs) are important constituents of the innate immunity system of all living organisms. They participate in the first line of defense against invading pathogens such as viruses, bacteria, and fungi. In view of the increasing difficulties to treat infectious diseases due to the emergence of antibiotic-resistant bacterial strains, AMPs have great potential to control infectious diseases in humans and animals. In this study, two small peptides, RcAlb-PepI and RcAlb-PepII, were designed based on the primary structure of Rc-2S-Alb, a 2S albumin from the seed cake of Ricinus communis, and their antimicrobial activity assessed. RcAlb-PepII strongly inhibited the growth of Klebsiella pneumoniae and Candida parapsilosis, and induced morphological alterations in their cell surface. C. parapsilosis exposed to RcAlb-PepII presented higher cell membrane permeabilization and elevated content of reactive oxygen species. RcAlb-PepII also degraded and reduced the biofilm formation in C. parapsilosis and in K. pneumonia cells. Experimentally, RcAlb-PepII was not hemolytic and had low toxicity to mammalian cells. These are advantageous characteristics, which suggest that RcAlb-PepII is safe and apparently effective for its intended use and has great potential for the future development of an antimicrobial agent with the ability to kill or inhibit K. pneumoniae and C. parapsilosis cells.


Assuntos
Anti-Infecciosos/farmacologia , Candida parapsilosis/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Ricinus/química , Albuminas , Anti-Infecciosos/síntese química , Peptídeos Catiônicos Antimicrobianos/síntese química , Biofilmes/efeitos dos fármacos , Candida parapsilosis/crescimento & desenvolvimento , Permeabilidade da Membrana Celular/efeitos dos fármacos , Desenho de Fármacos , Klebsiella pneumoniae/crescimento & desenvolvimento
15.
Mini Rev Med Chem ; 20(4): 308-330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31660809

RESUMO

2,4-Thiazolidinedione (2,4-TZD) is a versatile pharmacophore, a privileged scaffold, and a remarkable sulphur-containing heterocyclic compound with diverse pharmacological activities. The multifarious biological activities, due to different mechanisms of action, low cost, and easy availability of 2,4-TZD impressed medicinal chemists to integrate this moiety to develop various lead compounds with diverse therapeutic actions. This resulted in the swift development in the last decade for generating different new potential molecules bearing 2,4-TZD. In this review, the authors attempt to shape and present the latest investigations (2012 onwards) going on in generating promising 2,4-TZD containing lead compounds. The data has been collected and analyzed to develop the structure-activity relationship (SAR). The SAR and active pharmacophores of various leads accountable for antidiabetic, anticancer, antimicrobial, and antioxidant activities have also been illustrated. This review also highlighted some of the important chemical synthetic routes for the preparation of various 2,4-TZD derivatives. This review will definitely serve as a useful source of structural information to medicinal chemists and may be utilized for the strategic design of potent 2,4-TZD derivatives in the future.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Tiazolidinedionas/farmacologia , Animais , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antioxidantes/síntese química , Antioxidantes/química , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinedionas/síntese química , Tiazolidinedionas/química
16.
J Enzyme Inhib Med Chem ; 35(1): 59-64, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31663383

RESUMO

A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against ß-class CAs, herein we report an inhibition study with this class of compounds against ß-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for ß-class over human isozymes, making them interesting leads for the development of new anti-infectives.


Assuntos
Amidas/farmacologia , Anti-Infecciosos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Compostos Organometálicos/farmacologia , Ácidos Fosfóricos/farmacologia , Amidas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Fungos/efeitos dos fármacos , Fungos/enzimologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/enzimologia , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Ácidos Fosfóricos/química , Fósforo/química , Fósforo/farmacologia , Relação Estrutura-Atividade , Zinco/química , Zinco/farmacologia
17.
J Photochem Photobiol B ; 202: 111652, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31760374

RESUMO

The Biocompatibility and stability of nanoparticles using plants have been widely investigated due to its applications in the biomedical industry. Currently, there is a growing interest in nanoparticles in bone remodelling. Artemisia annua is an herbal plant commonly used in the treatment of various ailments. This study investigated the zinc oxide nanoparticles (ZnO NPs) using the green synthesis technique from A. annua and the effects of A. annua ZnO-NPs on osteoblast differentiation and inhibition of osteoclast formation. The formulated ZnO-NPs from A. annua were characterized by using various spectroscopic and microscopic methods Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray diffraction (XRD), and UV-Visible spectroscopy. The disc diffusion method was adopted to test the antimicrobial efficacy of ZnO-NPs. The viability of MG-63 cells were assayed by MTT test and Osteogenic-related assays like Real-time PCR and Mineralization assay were adopted to determine the effects of A. annua ZnO-NPs on the multiplication and differentiation of human osteoblast-like MG-63 cells. The characterization of A. annua ZnO-NPs revealed the crystalline nature with high zinc content and the presence of bioactive compounds from A. annua extract. The synthesized A. annua ZnO-NPs indicate significant antimicrobial potential. Besides, A. annua ZnO-NPs enhanced the proliferation, differentiation, and mineralization without causing significant cytotoxic impact on MG-63 cells. These effects indicate that A. annua ZnO-NPs can both stimulate bone formation via the differentiation of MG-63 cells. Hence, it was concluded that A. annua ZnO-NPs can be a promising agent for the treatment of bone deformities and bone-related diseases, however further research also required to explore the clear mechanism of A. annua ZnO-NPs in the formation and differentiation of MG-63 cells.


Assuntos
Artemisia annua/química , Diferenciação Celular , Proliferação de Células , Nanopartículas Metálicas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Artemisia annua/metabolismo , Cálcio/metabolismo , Candida/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Humanos , Nanopartículas Metálicas/toxicidade , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Casca de Planta/química , Casca de Planta/metabolismo , Extratos Vegetais/química , Óxido de Zinco/química
18.
Int J Biol Macromol ; 143: 952-957, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31743705

RESUMO

In this project, we have prepared a nanostructure of CeO2 nanorods, CoS2-CeO2, and CoS2-CeO2/cellulose-chitosan (CSCS) nanocomposites by ultrasonic method. This nanostructure was characterized using XRD, DLS, field emission scanning microscopy/EDS, DLS, UV-vis DRS, and PL spectrophotometer for determination of crystalline status, morphological, and bandgap data. Both the CeO2 and CoS2 show crystal structure with cubic and pyrite phase. It was found to be the crystal size of CeO2 nanorods, CoS2-CeO2 and CoS2-CeO2/CSCS were 56.19 nm, 62.11 nm, and 65.14 nm, respectively. The photocatalytic activity of CeO2 nanorods, CoS2-CeO2, and CoS2-CeO2/CSCS nanocomposites was evaluated with the photo-degradation of 4-nitrophenol (4NP) as a toxic organic pollutant under UV light irradiation. The 4NP photo-degradation amount reached 95.42% after 60 min UV light irradiation for CoS2-CeO2/CSCS nanocomposites due to the band gap data of CoS2-CeO2/CSCS was lower than other catalyst and photocatalytic modification process. The antimicrobial data indicated the significant properties of CoS2-CeO2/CSCS nanocomposites for this study.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Celulose/química , Cério/química , Quitosana/química , Cobalto/química , Nanocompostos/química , Processos Fotoquímicos , Anti-Infecciosos/síntese química , Catálise , Modelos Teóricos
19.
Eur J Pharm Sci ; 144: 105197, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862311

RESUMO

Antimicrobial resistance is one of the main global threats according to the World Health Organization's (WHO) report (World Health Organization 2014), therefore there is a need for the development of other agents, such as antimicrobial peptides (AMPs). Although AMPs are considered as major candidates for next-generation antibiotics, several challenges including low bioavailability, high manufacturing cost and toxicity are still to be solved for their practical use in therapeutic applications. Novel chemical modification approaches as well as strategies for their delivery offer several opportunities to overcome these barriers and develop more stable and cost-effective synthetic peptides with efficient delivery to the target site. The integration of the Quality by Design (QbD) approach in the early pharmaceutical developments supports researchers in optimizing the targeted product by a risk based manner. Peptide modifications and formulation of peptide delivery systems are challenging tasks and hide several risks. Understanding and evaluating the cause - effect relations within the initial Risk Assessment (RA) step in case of all attributes give the basis for the experimental design as the next step, and aids the formulation development in order to get the final product in the targeted quality range. This study presents a Quality by Design based antimicrobial peptide modification and formulation design. Analyses the potential risks in the AMP PEGylation process through the example of PGLa. The QbD based initial RA screened and evaluated the risk factors in this AMP modification procedure. The critical quality and process related factors were defined and their ranking was performed due to their estimated critical effect on the PEGylated AMP. This pre-formulation design study highlights the critical risk factors as decision points for the further steps.


Assuntos
Antibacterianos/síntese química , Anti-Infecciosos/síntese química , Desenho de Fármacos , Peptídeos/síntese química , Humanos , Nanopartículas , Medição de Risco
20.
Int J Biol Macromol ; 144: 441-448, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862374

RESUMO

The present study deals with novel synthesizing method of TEMPO oxidized cellulose (extracted from bagasse) (TOC) amino acids (l-phenyl alanine (Phe) and l-tryptophan (Trp)) nano-composites as potential antimicrobial biocompatible agents. The produced nanocomposites were characterized via Fourier transform Infrared (FT-IR) spectroscopy, thermal analysis (TGA and DTGA), scanning electron microscope(SEM), and transmission electron microscope (TEM) which approved that the synthesis of composites in nano-scale in spherical shape with average particle size 72 and 44.37 nm for l-phenylalanine composite (Phe-TOC) and l-tryptophan composite (Trp-TOC) respectively. The antimicrobial studies were carried out on (i) Gram-negative bacteria: Escherichia coli (NCTC-10416) and Pseudomonas aeruginosa (NCID-9016); (ii) Gram-positive bacteria: Streptococcus aurous (NCTC-7447) and Bacillus subtilis (NCID-3610); (iii) unicellular fungi: namely, Candida albicans (NCCLS 11). The results were cleared that the both composites have high effective, rapid and broad-spectrum antimicrobial activity. The Trp-TOC showed slightly higher antimicrobial activity than Phe-TOC especially in time required of killing performance. The Phe-TOC has required 20 h for killing all microbial population while Trp-TOC required only 12 h. The MIC values were close in both nanocomposites with high clear zone measurements in the same concentration in the case of Trp-TOC.


Assuntos
Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Celulose , Nanocompostos/química , Fenilalanina , Triptofano , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Celulose/química , Celulose/farmacologia , Fenilalanina/química , Fenilalanina/farmacologia , Triptofano/química , Triptofano/farmacologia
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