RESUMO
Two chitosan Schiff bases were synthesized by condensation of chitosan with 2-(4-formylphenoxy)-N-phenylacetamide and N-(4-bromophenyl)-2-(4-formylphenoxy) acetamide denoted as Cs-SBA and Cs-SBBr, respectively. The molecular structures of the resulting chitosan derivatives were characterized using FTIR and 1HNMR and their thermal properties were investigated by TGA. These derivatives were treated with sodium tripolyphosphate (TPP) to produce Cs Schiff base nanoparticles. The nanoparticles physicochemical properties were determined by FTIR, XRD, TEM, and zeta potential analysis. The antimicrobial action against Helicobacter pylori (H. pylori) was evaluated and the results indicated that the anti-H. pylori activity had minimal inhibitory concentration MIC values of 15.62 ± 0.05 and 3.9 ± 0.03 µg/mL for Cs-SBA and Cs-SBBr nanoparticles (Cs-SBA NPs and Cs-SBBr NPs), respectively. The better biologically active nanoparticles, Cs-SBBr NPs, were tested for their cyclooxygenases (COX-1 and COX-2) inhibitory potential. Cs-SBBr NPs demonstrated COX enzyme inhibition activity against COX-2 (IC50 4.5 ± 0.165 µg/mL) higher than the conventional Indomethacin (IC50 0.08 ± 0.003 µg/mL), and Celecoxib (IC50 0.79 ± 0.029 µg/mL). Additionally, the cytotoxicity test of Cs-SBBr NPs showed cytotoxic effect on Vero cells (CCL-81) with IC50 = 17.95 ± 0.12 µg/mL which is regarded as a safe compound. Therefore, Cs-SBBr NPs may become an alternative to cure H. pylori and prevent gastric cancer.
Assuntos
Antibacterianos , Quitosana , Helicobacter pylori , Nanopartículas , Bases de Schiff , Quitosana/química , Quitosana/farmacologia , Quitosana/síntese química , Helicobacter pylori/efeitos dos fármacos , Bases de Schiff/química , Bases de Schiff/farmacologia , Nanopartículas/química , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Testes de Sensibilidade Microbiana , Células Vero , Chlorocebus aethiops , Técnicas de Química Sintética , Inibidores de Ciclo-Oxigenase/farmacologia , Inibidores de Ciclo-Oxigenase/química , Inibidores de Ciclo-Oxigenase/síntese química , Ciclo-Oxigenase 2/metabolismoRESUMO
The production of novel natural medicines for the treatment of Helicobacter pylori (H. pylori) has lately attracted a lot of interest. Some bacterial infections have traditionally been alleviated by terpenes. The present work intended to examine the impact of several chitosan menthone Schiff base nanocomposites on the treatment of H. pylori infection as well as on its anti-inflammatory capacity. Chitosan (Cs) was condensed with menthone with different molar ratios of Cs:menthone (1:0.5, 1:1, and 1:2) to produce chitosan Schiff bases namely; Cs-SB1, Cs-SB2, and Cs-SB3, respectively. Cs-SB3 Schiff base nanocomposites were prepared individually by adding 2%Ag, 2%Se, (1%Ag + 1%Se), and 2%Fe2O3 nanoparticles to produce compounds denoted as Cs-SB-Ag, Cs-SB-Se, Cs-SB-Ag/ Se, and Cs-SB-Fe, respectively. The anti-H. pylori activity of Cs-SB-Se was detected at a minimal inhibitory concentration MIC of 1.9 µg/mL making it the most biologically active compound in our study. Cs-SB-Se nanocomposite was tested for its cyclooxygenases (COX-1 and COX-2) inhibitory potential which demonstrated inhibitory efficacy towards COX enzymes with inhibition value against COX-1 (IC50 = 49.86 ± 1.784 µg/mL) and COX-2 (IC50 = 12.64 ± 0.463 µg/mL) which were less than the well-known Celecoxib (22.65 ± 0.081 and 0.789 ± 0.029 µg/mL) and Indomethacin (0.035 ± 0.001 and 0.08 ± 0.003 µg/mL) inhibitors. The selectivity index SI = 3.94 for tested nanocomposites indicated higher selectivity for COX-1. The cytotoxicity of the Cs-SB-Se nanocomposite was evaluated in Vero cells (CCL-81) and it showed that at a concentration of 62.5 µg/mL, cell viability was 85.43 %.
Assuntos
Quitosana , Helicobacter pylori , Mentol , Nanocompostos , Nanopartículas , Animais , Chlorocebus aethiops , Quitosana/farmacologia , Bases de Schiff/farmacologia , Células Vero , Ciclo-Oxigenase 2 , Antibacterianos/farmacologiaRESUMO
Anti-cancer medications that are delivered specifically to the tumor site possess greater efficacy with less negative effects on the body. So, the current research relies on a novel method for intercalating the anticancer medication methotrexate in poly(3-hydroxybutyrate)/chitosan-graft poly (acrylic acid) conjugated with sodium hyaluronate. The graft copolymers were synthesized through persulfate-initiated grafting of acrylic acid onto a binary mixture of various amounts of chitosan and poly(3-hydroxybutyrate) (2/1, 1/1 and 1/2, w/w) using microwave irradiation. The graft copolymer was conjugated with sodium hyaluronate for targeted delivery of methotrexate drug specifically to colon cancer cell lines (Caco-2). The graft copolymers were characterized by many physical techniques. The maximum drug loading efficiency was observed in case of the graft copolymer/hyaluronate rich in chitosan content 69.7 ± 2.7 % (4.65 mg/g) with a sustained release about 98.6 ± 1.12 %, at pH 7.4. The findings of severe cytotoxicity having a value of the IC50 of 11.7 µg/ml, a substantial proportion of apoptotic cells (67.88 %), and an elevated level of DNA breakage inside the treated Caco-2 cells verified the effective release of methotrexate from the loaded copolymer matrix. Besides, the high stability and biological activity of the released drug was exhibited through occurrence of greater increment of reactive oxygen species and effect on the extent of expression of genes connected to apoptosis and anti-oxidant enzymes within the treated cells. Ultimately, this system can be recommended as potent carrier for methotrexate administration to targeted cancerous cells in the colon.
Assuntos
Quitosana , Neoplasias do Colo , Humanos , Metotrexato/farmacologia , Preparações Farmacêuticas , Ácido 3-Hidroxibutírico , Ácido Hialurônico , Células CACO-2 , Polímeros , Neoplasias do Colo/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Portadores de FármacosRESUMO
Chitosan (Cs) bis-aldehyde Schiff base derivatives were synthesized by condensation of Cs with three bis-aldehydes namely; butane-1,4-diyl bis(4-formylbenzoate), N,N'-(butane-1,4-diyl)bis(2-(4-formylphenoxy)acetamide) and 4,4'-(butane-1,4-diylbis(oxy))dibenzaldehyde. The prepared Cs derivatives were blended with carboxymethyl chitosan(CMC) and graphene quantum dots (GQDs) to produce semi-IPNs polyelectrolyte complexes (PECs). and characterized with respect to their molecular structure and physio-chemical properties. The antibacterial activity against H. pylori (and in vitro Inosine 5'-monophosphate dehydrogenase IMPDH inhibitory assay) was evaluated. Additionally, a preliminary in vitro assessment for wound healing was performed against PECs in which wound closure percentages, and rates were investigated indicating an accelerated wound healing compared with untreated cells. The PEC based on Schiff base PEC containing amide linkage showed the highest wound healing ability. A minimal inhibitory concentration (MIC) was obtained for the PEC sample containing Cs Schiff base derived from 4,4'-(butane-1, 4-diylbis(oxy))dibenzaldehyde at a dose of 0.98 µg/ml inhibiting H. pylori growth by 100%. Additionally, the selected above-mentioned compound was selected to test its inhibitory activity against the HpIMPDH enzyme in addition to its selectivity towards the hIMPDH2 enzyme and was found to have promising activity against the HpIMPDH enzyme with IC50 value of 0.65 µM, and to be safer and less active against the hIMPDH2 enzyme with IC50 > 10 µM, reflecting its selectivity.
Assuntos
Quitosana , Grafite , Helicobacter pylori , Pontos Quânticos , Antibacterianos/química , Antibacterianos/farmacologia , Butanos , Quitosana/química , IMP Desidrogenase , Polieletrólitos , Estudos Prospectivos , Bases de Schiff/químicaRESUMO
Three heteroaryl pyrazole derivatives; namely 1-phenyl-3-(thiophene-2-yl)-1H-pyrazole-4-carbaldehyde, 1-phenyl-3-(furan-2-yl)-1H-pyrazole-4-carbaldehyde and 1-phenyl-3-(pyridine-3-yl)-1H-pyrazole-4-carbaldehyde were synthesized and reacted with chitosan to form Schiff bases of chitosan. All newly synthesized compounds have been characterized by solubility tests, elemental analysis, spectral (FTIR, 1H NMR) analyses, thermogravimetric analysis and X-ray diffraction (XRD). The Schiff bases were screened for their biological activity against gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans) and fungi (Asperagillus fumigatus and Candida albican). The results indicated that the antimicrobial activity was dependent on the type of the Schiff base moiety. Cytotoxicity of the prepared chitosan derivatives was evaluated by MTT assay and the results indicated the absence of cytotoxic activity.